|
1
|
Seo JH, Kim WK, Kang KW, Lee S, Kang BJ. Anti-inflammatory effects of polydeoxyribonucleotide and adipose tissue-derived mesenchymal stem cells in a canine cell model of osteoarthritis. J Vet Sci 2024; 25:e68. [PMID: 39363656 PMCID: PMC11450397 DOI: 10.4142/jvs.24147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 07/24/2024] [Accepted: 08/14/2024] [Indexed: 10/05/2024] Open
Abstract
IMPORTANCE A relatively new therapeutic agent for osteoarthritis (OA), polydeoxyribonucleotide (PDRN), shows potential in treating human OA due to its regenerative and anti-inflammatory effects. However, studies on PDRN for canine OA are limited, and no study has investigated their use with mesenchymal stem cells (MSCs) conventionally used for OA treatment. OBJECTIVE This study aimed to evaluate the potential of PDRN and explore its combined effect with adipose tissue-derived MSCs (AdMSCs) in treating canine OA. METHODS To study the impact of PDRN, canine chondrocytes, synoviocytes, and AdMSCs were exposed to various PDRN concentrations, and viability was assessed using cell counting kit-8. The OA model was created by treating chondrocytes and synoviocytes with lipopolysaccharide, followed by treatment under three different conditions: PDRN alone, AdMSCs alone, and a combination of PDRN and AdMSCs. Using real-time quantitative polymerase chain reaction, the anti-inflammatory effects and mechanisms were investigated by quantitatively assessing pro-inflammatory cytokines, collagen degradation markers, adenosine A2a receptor (ADORA2A), and nuclear factor-kappa B. RESULTS PDRN alone and combined with AdMSCs significantly reduced the expression of pro-inflammatory cytokines and collagen degradation markers in an OA model. PDRN promoted AdMSC proliferation and upregulated ADORA2A expression. AdMSCs exhibited comprehensive anti-inflammatory effects through paracrine effects, and both substances reduced inflammatory gene expression through different mechanisms, potentially enhancing therapeutic effects. CONCLUSIONS AND RELEVANCE The results indicate that PDRN is a safe and effective anti-inflammatory material that can be used independently or as an adjuvant for AdMSCs. Although additional research is necessary, this study is significant because it provides a foundation for future research at the cellular level.
Collapse
Affiliation(s)
- Ju-Hui Seo
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea
| | - Woo Keyoung Kim
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea
- BK21 FOUR Future Veterinary Medicine Leading Education and Research Center, Seoul National University, Seoul 08826, Korea
| | - Kyu-Won Kang
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea
| | - Seoyun Lee
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea
- BK21 FOUR Future Veterinary Medicine Leading Education and Research Center, Seoul National University, Seoul 08826, Korea
| | - Byung-Jae Kang
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea
- BK21 FOUR Future Veterinary Medicine Leading Education and Research Center, Seoul National University, Seoul 08826, Korea.
| |
Collapse
|
|
2
|
Khasawneh RR, Abu-El-Rub E, Almahasneh FA, Alzu'bi A, Zegallai HM, Almazari RA, Magableh H, Mazari MH, Shlool HF, Sanajleh AK. Addressing the impact of high glucose microenvironment on the immunosuppressive characteristics of human mesenchymal stem cells. IUBMB Life 2024; 76:286-295. [PMID: 38014654 DOI: 10.1002/iub.2796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 11/05/2023] [Indexed: 11/29/2023]
Abstract
Mesenchymal stem cells (MSCs) are a therapeutically efficient type of stem cells validated by their ability to treat many inflammatory and chronic conditions. The biological and therapeutic characteristics of MSCs can be modified depending on the type of microenvironment at the site of transplantation. Diabetes mellitus (DM) is a commonly diagnosed metabolic disease characterized by hyperglycemia, which alters over time the cellular and molecular functions of many cells and causes their damage. Hyperglycemia can also impact the success rate of MSCs transplantation; therefore, it is extremely significant to investigate the effect of high glucose on the biological and therapeutic attributes of MSCs, particularly their immunomodulatory abilities. Thus, in this study, we explored the effect of high glucose on the immunosuppressive characteristics of human adipose tissue-derived mesenchymal stem cells (hAD-MSCs). We found that hAD-MSCs cultured in high glucose lost their immunomodulatory abilities and became detectable by immune cells. The decline in the immunosuppressive capabilities of hAD-MSCs was mediated by significant decrease in the levels of IDO, IL-10, and complement factor H and substantial increase in the activity of immunoproteasome. The protein levels of AMP-activated protein kinase (AMPK) and phosphofructokinase-1 (PFK-1), which are integral regulators of glycolysis, revealed a marked decline in high glucose exposed MSCs. The findings of our study indicated the possibility of immunomodulatory shift in MSCs after being cultured in high glucose, which can be translationally employed to explain their poor survival and short-lived therapeutic outcomes in diabetic patients.
Collapse
Affiliation(s)
- Ramada R Khasawneh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Ejlal Abu-El-Rub
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Fatimah A Almahasneh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Ayman Alzu'bi
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Hana M Zegallai
- Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, Children's Hospital Research Institute of Manitoba, Department of Pharmacology & Therapeutics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
| | - Rawan A Almazari
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Huthaifa Magableh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Mohammad H Mazari
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Haitham F Shlool
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Ahmad K Sanajleh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| |
Collapse
|
|
3
|
Almahasneh F, Abu-El-Rub E, Khasawneh RR, Almazari R. Effects of high glucose and severe hypoxia on the biological behavior of mesenchymal stem cells at various passages. World J Stem Cells 2024; 16:434-443. [PMID: 38690519 PMCID: PMC11056633 DOI: 10.4252/wjsc.v16.i4.434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 02/05/2024] [Accepted: 03/18/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) have been extensively studied for therapeutic potential, due to their regenerative and immunomodulatory properties. Serial passage and stress factors may affect the biological characteristics of MSCs, but the details of these effects have not been recognized yet. AIM To investigate the effects of stress factors (high glucose and severe hypoxia) on the biological characteristics of MSCs at different passages, in order to optimize the therapeutic applications of MSCs. METHODS In this study, we investigated the impact of two stress conditions; severe hypoxia and high glucose on human adipose-tissue derived MSCs (hAD-MSCs) at passages 6 (P6), P8, and P10. Proliferation, senescence and apoptosis were evaluated measuring WST-1, senescence-associated beta-galactosidase, and annexin V, respectively. RESULTS Cells at P6 showed decreased proliferation and increased apoptosis under conditions of high glucose and hypoxia compared to control, while the extent of senescence did not change significantly under stress conditions. At P8 hAD-MSCs cultured in stress conditions had a significant decrease in proliferation and apoptosis and a significant increase in senescence compared to counterpart cells at P6. Cells cultured in high glucose at P10 had lower proliferation and higher senescence than their counterparts in the previous passage, while no change in apoptosis was observed. On the other hand, MSCs cultured under hypoxia showed decreased senescence, increased apoptosis and no significant change in proliferation when compared to the same conditions at P8. CONCLUSION These results indicate that stress factors had distinct effects on the biological processes of MSCs at different passages, and suggest that senescence may be a protective mechanism for MSCs to survive under stress conditions at higher passage numbers.
Collapse
Affiliation(s)
- Fatimah Almahasneh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan
| | - Ejlal Abu-El-Rub
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan.
| | - Ramada R Khasawneh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan
| | - Rawan Almazari
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan
| |
Collapse
|
|
4
|
Wang Q, Li Y, Yuan H, Peng L, Dai Z, Sun Y, Liu R, Li W, Li J, Zhu C. Hypoxia preconditioning of human amniotic mesenchymal stem cells enhances proliferation and migration and promotes their homing via the HGF/C-MET signaling axis to augment the repair of acute liver failure. Tissue Cell 2024; 87:102326. [PMID: 38442547 DOI: 10.1016/j.tice.2024.102326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 01/17/2024] [Accepted: 02/06/2024] [Indexed: 03/07/2024]
Abstract
BACKGROUND Transplantation of mesenchymal stem cells (MSCs) is a newly developed strategy for treating acute liver failure (ALF). Nonetheless, the low survival rate of MSCs after transplantation and their poor homing to damaged tissues limit the clinical application of MSCs. The research assessed whether hypoxic preconditioning (HPC) can improve the biological activity of human amniotic mesenchymal stem cells (hA-MSCs), promote their homing ability to the liver of mice with ALF, and influence liver tissue repair. METHODS Flow cytometry, CCK8, Transwell, and Western blotting assays were conducted to assess the effects of hypoxic preconditioning on the phenotype, proliferation, and migration of hA-MSCs and the changes in the c-Met and CXCR4 gene expression levels were studied. To evaluate the effects of the transplantation of hypoxic preconditioning of hA-MSCs on the homing and repair of D-galactosamine (D-GalN)/LPS-induced ALF, the mechanism was elucidated by adding c-Met, CXCR4-specific blockers (SU11274 and AMD3100). RESULTS After hypoxia pretreatment (1% oxygen volume fraction), hA-MSCs maintained the morphological characteristics of adherence and vortex colony growth and showed high CD44, CD90, and CD105 and low CD31, CD34, and CD45 expression levels. Hypoxic preconditioning of hA-MSCs significantly increased their proliferation and migration and highly expressed the c-Met and CXCR4 genes. In vivo and in vitro, this migration-promoting effect was suppressed by the c-Met specific blocker SU11274. In the acute liver failure mouse model, the HGF expression level was considerably elevated in the liver than that in the serum, lungs and kidneys. The transplantation of hypoxic preconditioned hA-MSCs introduced a remarkable improvement in the liver function and survival rate of mice with ALF and enhanced the anti-apoptosis ability of liver cells. The anti-apoptotic enhancing effect of hypoxic preconditioning was suppressed by the c-Met specific blocker SU11274. Hypoxic hA-MSCs administration was observed to have considerably increased the fluorescent cells in the liver than that recorded after administering normal oxygen-hA-MSCs. The number of hepatic fluorescent cells decreased remarkably after adding the c-Met inhibitor SU11274, compared to that recorded after hypoxic pretreatment, whereas the effect of c-Met inhibitor SU11274 on normal oxygen-hA-MSCs was not significant. CONCLUSIONS Hypoxic preconditioning depicted no impact on the morphology and phenotype features of the human amniotic mesenchymal stem cells, but it can promote their proliferation, migration, anti-apoptotic effect, and homing rate and improve the repair of acute liver failure, which might be mediated by the HGF/c-Met signaling axis.
Collapse
Affiliation(s)
- Qian Wang
- Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yuwen Li
- Department of Pediatrics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hui Yuan
- Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Linya Peng
- Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zixing Dai
- Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ye Sun
- Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Rui Liu
- Department of Infectious and Tropical Diseases, The Second Affiliated Hospital of Hainan Medical University, Hainan, China
| | - Wenting Li
- Department of Infectious and Tropical Diseases, The Second Affiliated Hospital of Hainan Medical University, Hainan, China
| | - Jun Li
- Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
| | - Chuanlong Zhu
- Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Infectious and Tropical Diseases, The Second Affiliated Hospital of Hainan Medical University, Hainan, China.
| |
Collapse
|
|
5
|
Zare F, Ghafouri-Fard S, Shamosi A, Pahlavan S, Mahboudi H, Tavasoli A, Eslami S. Oleoylethanolamide protects mesenchymal stem/stromal cells (MSCs) from oxidative stress and reduces adipogenic related genes expression in adipose-derived MSCs undergoing adipocyte differentiation. Mol Biol Rep 2023; 51:33. [PMID: 38155334 DOI: 10.1007/s11033-023-08929-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 10/24/2023] [Indexed: 12/30/2023]
Abstract
BACKGROUND Human mesenchymal stem/stromal cells (hMSCs) are known for their pronounced therapeutic potential; however, they are still applied in limited clinical cases for several reasons. ROS-mediated oxidative stress is among the chief causes of post-transplantation apoptosis and death of hMSCs. It has been reported that a strategy to protect hMSCs against ROS is to pretreat them with antioxidants. Oleoylethanolamide (OEA) is a monounsaturated fatty acid derived from oleic acid and it has many protective properties, including anti-obesity, anti-inflammatory, and antioxidant effects. OEA is also used as a weight loss supplement; due to its high affinity for the PPAR-α receptor, OEA increases the fat metabolism rate. METHODS AND RESULTS This study hence assessed the effects of OEA pretreatment on the in vitro survival rate and resistance of hMSCs under oxidative stress as well as the cellular and molecular events in the biology of stem/stromal cells affected by oxidative stress and free radicals. Considering the role of MSCs in adipogenesis and obesity, the expression of the main genes involved in adipogenesis was also addressed in this study. Results revealed that OEA increases the in vitro proliferation of MSCs and inhibits cell apoptosis by reducing the induction of oxidative stress. The results also indicated that OEA exerts its antioxidant properties by both activating the Nrf2/NQO-1/HO-1 signaling pathway and directly combating free radicals. Moreover, OEA can reduce adipogenesis through reducing the expression of PPARγ, leptin and CEBPA genes in hMSCs undergoing adipocyte differentiation. CONCLUSIONS Thus, OEA protects hMSCs from oxidative stress and reduces adipogenic related genes expression and can be regarded as a therapeutic agent for this purpose.
Collapse
Affiliation(s)
- Fereshteh Zare
- Student Research Committee, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Soudeh Ghafouri-Fard
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atefeh Shamosi
- Department of Anatomy, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Shahrzad Pahlavan
- Department of Anatomy, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Hossein Mahboudi
- Department of Biotechnology, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran
| | - Afsaneh Tavasoli
- Department of Biotechnology, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran
| | - Solat Eslami
- Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran.
- Department of Medical Biotechnology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
| |
Collapse
|
|
6
|
Suwanmanee G, Tantrawatpan C, Kheolamai P, Paraoan L, Manochantr S. Fucoxanthin diminishes oxidative stress damage in human placenta-derived mesenchymal stem cells through the PI3K/Akt/Nrf-2 pathway. Sci Rep 2023; 13:22974. [PMID: 38151503 PMCID: PMC10752906 DOI: 10.1038/s41598-023-49751-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 12/12/2023] [Indexed: 12/29/2023] Open
Abstract
Placenta-derived mesenchymal stem cells (PL-MSCs) have therapeutic potential in various clinical contexts due to their regenerative and immunomodulatory properties. However, with increasing age or extensive in vitro culture, their viability and function are gradually lost, thus restricting their therapeutic application. The primary cause of this deterioration is oxidative injury from free radicals. Therefore, enhancing cell viability and restoring cellular repair mechanisms of PL-MSCs in an oxidative stress environment are crucial in this context. Fucoxanthin, a carotenoid derived from brown seaweed, demonstrates antioxidant activity by increasing the production of antioxidant enzymes and lowering the levels of reactive oxygen species (ROS). This study aimed to determine whether fucoxanthin protects PL-MSCs from hydrogen peroxide (H2O2)-induced oxidative stress. After characterization, PL-MSCs were co-treated with fucoxanthin and H2O2 for 24 h (co-treatment) or pre-treated with fucoxanthin for 24 h followed by H2O2 for 24 h (pre-treatment). The effects of fucoxanthin on cell viability and proliferation were examined using an MTT assay. The expression of antioxidant enzymes, PI3K/Akt/Nrf-2 and intracellular ROS production were investigated in fucoxanthin-treated PL-MSCs compared to the untreated group. The gene expression and involvement of specific pathways in the cytoprotective effect of fucoxanthin were investigated by high-throughput NanoString nCounter analysis. The results demonstrated that co-treatment and pre-treatment with fucoxanthin restored the viability and proliferative capacity of PL-MSCs. Fucoxanthin treatment increased the expression of antioxidant enzymes in PL-MSCs cultured under oxidative stress conditions and decreased intracellular ROS accumulation. Markedly, fucoxanthin treatment could restore PI3K/Akt/Nrf-2 expression in H2O2-treated PL-MSCs. High-throughput analysis revealed up-regulation of genes involved in cell survival pathways, including cell cycle and proliferation, DNA damage repair pathways, and down-regulation of genes in apoptosis and autophagy pathways. This study demonstrated that fucoxanthin protects and rescues PL-MSCs from oxidative stress damage through the PI3K/Akt/Nrf-2 pathway. Our data provide the supporting evidence for the use of fucoxanthin as an antioxidant cytoprotective agent to improve the viability and proliferation capacity of PL-MSCs both in vitro and in vivo required to increase the effectiveness of MSC expansion for therapeutic applications.
Collapse
Affiliation(s)
- Gunticha Suwanmanee
- Division of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani, 12120, Thailand
| | - Chairat Tantrawatpan
- Division of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani, 12120, Thailand
- Center of Excellence in Stem Research and Innovation, Thammasat University, Pathumthani, 12120, Thailand
| | - Pakpoom Kheolamai
- Division of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani, 12120, Thailand
- Center of Excellence in Stem Research and Innovation, Thammasat University, Pathumthani, 12120, Thailand
| | - Luminita Paraoan
- Department of Biology, Faculty of Arts and Sciences, Edge Hill University, BioSciences Building, St Helens Road, Ormskirk, L39 4QP, UK
| | - Sirikul Manochantr
- Division of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani, 12120, Thailand.
- Center of Excellence in Stem Research and Innovation, Thammasat University, Pathumthani, 12120, Thailand.
| |
Collapse
|
|
7
|
McLoughlin ST, McKenna AR, Fisher JP. 4D Bioprinting via Molecular Network Contraction for Membranous Tissue Fabrication. Adv Healthc Mater 2023; 12:e2300642. [PMID: 37463127 DOI: 10.1002/adhm.202300642] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 06/29/2023] [Accepted: 07/08/2023] [Indexed: 07/20/2023]
Abstract
Generation of thin membranous tissues (TMT), such as the cornea, epidermis, and periosteum, presents a difficult fabrication challenge in tissue engineering (TE). TMTs consist of several cell layers that are less than 100 µm in thickness per layer. While traditional methods provide the necessary resolution for TMT fabrication, they require significant handling and incorporation of several layers is limited. Extrusion bioprinting offers precise control over deposition of different biomaterials and cell populations within the same construct but lacks the resolution to generate biomimetic TMTs. For the first time, a 4D bioprinting strategy that allows for the generation of cell-laden TMTs is developed. Anionic gelatin methacrylate (GelMA) hydrogels are treated with cationic poly-l-lysine (PLL), which induces charge attraction, microscale network collapse, and macroscale hydrogel shrinking. The impact of shrinking on hydrogel properties, print resolution, and cell viability is presented. Additionally, this work suggests that a novel mechanism is occurring, where PLL exhibits a contractile force on GelMA and PLL molecular weight drives GelMA shrinking capabilities. Finally, it is shown that this phenomenon can occur while maintaining an encapsulated cell population. These findings address a critical barrier by generating macroscale tissue structures with their microscale TMT counterparts in the same print.
Collapse
Affiliation(s)
- Shannon T McLoughlin
- Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, MD, 20742, USA
| | - Abigail R McKenna
- Center for Engineering Complex Tissues, University of Maryland, College Park, MD, 20742, USA
- Department of Biology, University of Maryland, College Park, MD, 20742, USA
| | - John P Fisher
- Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA
- Center for Engineering Complex Tissues, University of Maryland, College Park, MD, 20742, USA
| |
Collapse
|
|
8
|
Kahrizi MS, Mousavi E, Khosravi A, Rahnama S, Salehi A, Nasrabadi N, Ebrahimzadeh F, Jamali S. Recent advances in pre-conditioned mesenchymal stem/stromal cell (MSCs) therapy in organ failure; a comprehensive review of preclinical studies. Stem Cell Res Ther 2023; 14:155. [PMID: 37287066 DOI: 10.1186/s13287-023-03374-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 05/10/2023] [Indexed: 06/09/2023] Open
Abstract
Mesenchymal stem/stromal cells (MSCs)-based therapy brings the reassuring capability to regenerative medicine through their self-renewal and multilineage potency. Also, they secret a diversity of mediators, which are complicated in moderation of deregulated immune responses, and yielding angiogenesis in vivo. Nonetheless, MSCs may lose biological performance after procurement and prolonged expansion in vitro. Also, following transplantation and migration to target tissue, they encounter a harsh milieu accompanied by death signals because of the lack of proper tensegrity structure between the cells and matrix. Accordingly, pre-conditioning of MSCs is strongly suggested to upgrade their performances in vivo, leading to more favored transplantation efficacy in regenerative medicine. Indeed, MSCs ex vivo pre-conditioning by hypoxia, inflammatory stimulus, or other factors/conditions may stimulate their survival, proliferation, migration, exosome secretion, and pro-angiogenic and anti-inflammatory characteristics in vivo. In this review, we deliver an overview of the pre-conditioning methods that are considered a strategy for improving the therapeutic efficacy of MSCs in organ failures, in particular, renal, heart, lung, and liver.
Collapse
Affiliation(s)
| | - Elnaz Mousavi
- Department of Endodontics, School of Dentistry, Guilan University of Medical Sciences, Rasht, Iran
| | - Armin Khosravi
- Department of Periodontics, Dental School, Islamic Azad University, Isfahan (Khorasgan) Branch, Isfahan, Iran
| | - Sara Rahnama
- Department of Pediatric Dentistry, School of Dentistry, Semnan University of Medical Sciences, Semnan, Iran
| | - Ali Salehi
- Department of Oral and Maxillofacial Radiology, School of Dentistry, Islamic Azad University, Isfahan (Khorasgan) Branch, Isfahan, Iran
| | - Navid Nasrabadi
- Department of Endodontics, School of Dentistry, Birjand University of Medical Sciences, Birjand, Iran
| | - Farnoosh Ebrahimzadeh
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Samira Jamali
- Department of Endodontics, Stomatological Hospital, College of Stomatology, Xi'an Jiaotong University, Shaanxi, People's Republic of China.
| |
Collapse
|
|
9
|
Rahimi B, Panahi M, Lotfi H, Khalili M, Salehi A, Saraygord-Afshari N, Alizadeh E. Sodium selenite preserves rBM-MSCs' stemness, differentiation potential, and immunophenotype and protects them against oxidative stress via activation of the Nrf2 signaling pathway. BMC Complement Med Ther 2023; 23:131. [PMID: 37098557 PMCID: PMC10127330 DOI: 10.1186/s12906-023-03952-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 04/10/2023] [Indexed: 04/27/2023] Open
Abstract
BACKGROUND The physiological level of reactive oxygen species (ROS) is necessary for many cellular functions. However, during the in-vitro manipulations, cells face a high level of ROS, leading to reduced cell quality. Preventing this abnormal ROS level is a challenging task. Hence, here we evaluated the effect of sodium selenite supplementation on the antioxidant potential, stemness capacity, and differentiation of rat-derived Bone Marrow MSCs (rBM-MSCs) and planned to check our hypothesis on the molecular pathways and networks linked to sodium selenite's antioxidant properties. METHODS MTT assay was used to assess the rBM-MSCs cells' viability following sodium selenite supplementation (concentrations of: 0.001, 0.01, 0.1, 1, 10 µM). The expression level of OCT-4, NANOG, and SIRT1 was explored using qPCR. The adipocyte differentiation capacity of MSCs was checked after Sodium Selenite treatment. The DCFH-DA assay was used to determine intracellular ROS levels. Sodium selenite-related expression of HIF-1α, GPX, SOD, TrxR, p-AKT, Nrf2, and p38 markers was determined using western blot. Significant findings were investigated by the String tool to picture the probable molecular network. RESULTS Media supplemented with 0.1 µM sodium selenite helped to preserve rBM-MSCs multipotency and keep their surface markers presentation; this also reduced the ROS level and improved the rBM-MSCs' antioxidant and stemness capacity. We observed enhanced viability and reduced senescence for rBM-MSCs. Moreover, sodium selenite helped in rBM-MSCs cytoprotection by regulating the expression of HIF-1 of AKT, Nrf2, SOD, GPX, and TrxR markers. CONCLUSIONS We showed that sodium selenite could help protect MSCs during in-vitro manipulations, probably via the Nrf2 pathway.
Collapse
Affiliation(s)
- Bahareh Rahimi
- Department of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical Sciences (IUMS), Shahid Hemmat Highway, Tehran, 1449614535, Iran
| | - Mohammad Panahi
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hajie Lotfi
- Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Mostafa Khalili
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Astireh Salehi
- Biology Department, Islamic Azad University, Sanandaj Branch, Sanandaj, Iran
| | - Neda Saraygord-Afshari
- Department of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical Sciences (IUMS), Shahid Hemmat Highway, Tehran, 1449614535, Iran.
| | - Effat Alizadeh
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| |
Collapse
|
|
10
|
Lopes-Pacheco M, Rocco PRM. Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases. Front Pharmacol 2023; 14:1067422. [PMID: 37007034 PMCID: PMC10062457 DOI: 10.3389/fphar.2023.1067422] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
Respiratory diseases remain a major health concern worldwide because they subject patients to considerable financial and psychosocial burdens and result in a high rate of morbidity and mortality. Although significant progress has been made in understanding the underlying pathologic mechanisms of severe respiratory diseases, most therapies are supportive, aiming to mitigate symptoms and slow down their progressive course but cannot improve lung function or reverse tissue remodeling. Mesenchymal stromal cells (MSCs) are at the forefront of the regenerative medicine field due to their unique biomedical potential in promoting immunomodulation, anti-inflammatory, anti-apoptotic and antimicrobial activities, and tissue repair in various experimental models. However, despite several years of preclinical research on MSCs, therapeutic outcomes have fallen far short in early-stage clinical trials for respiratory diseases. This limited efficacy has been associated with several factors, such as reduced MSC homing, survival, and infusion in the late course of lung disease. Accordingly, genetic engineering and preconditioning methods have emerged as functional enhancement strategies to potentiate the therapeutic actions of MSCs and thus achieve better clinical outcomes. This narrative review describes various strategies that have been investigated in the experimental setting to functionally potentiate the therapeutic properties of MSCs for respiratory diseases. These include changes in culture conditions, exposure of MSCs to inflammatory environments, pharmacological agents or other substances, and genetic manipulation for enhanced and sustained expression of genes of interest. Future directions and challenges in efficiently translating MSC research into clinical practice are discussed.
Collapse
Affiliation(s)
- Miquéias Lopes-Pacheco
- Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, Lisbon, Portugal
- *Correspondence: Miquéias Lopes-Pacheco, ; Patricia R. M. Rocco,
| | - Patricia R. M. Rocco
- Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- *Correspondence: Miquéias Lopes-Pacheco, ; Patricia R. M. Rocco,
| |
Collapse
|
|
11
|
Mousavi E, Khosravi A, Sedigh SS, Mayanei SAT, Banakar M, Karimzadeh M, Fathi A. Exosomes derived from mesenchymal stem cells: Heralding a new treatment for periodontitis? Tissue Cell 2023; 82:102070. [PMID: 37004268 DOI: 10.1016/j.tice.2023.102070] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 02/24/2023] [Accepted: 03/12/2023] [Indexed: 03/16/2023]
Abstract
Periodontitis, as a complex inflammatory disorder, is characterized by continuous destruction of the teeth-supporting components, like alveolar bone and periodontal ligament, and affects a great percentage of individuals over the world. Also, this oral disease is linked with multiple serious illnesses, e.g., cardiovascular disorders, diabetes, and oral cancer; thus, exerting efficient therapy for periodontitis is necessary. Unfortunately, the current therapies for the disease (e.g., surgical and nonsurgical methods) have not reflected enough effectiveness against periodontitis. At present, mesenchymal stem cell (MSC)-based remedy has created new hope for curating different diseases; however, MSCs have no capability to engraft into the chosen tissue, and the tumorigenic influences of MSCs are still the main concern. Interestingly, documents have revealed that MSC-derived mediators, like exosomes, which their exploitation is more feasible than intact MSCs, can be an effective therapeutic candidate for periodontitis. Therefore, in this study, we will review evidence in conjunction with their possible curative impacts on periodontitis cases.
Collapse
Affiliation(s)
- Elnaz Mousavi
- Dental Sciences Research Center, Department of Endodontics, School of Dentistry, Guilan University of Medical Sciences, Rasht, Iran
| | - Armin Khosravi
- Department of Periodontics, Dental School, Islamic Azad University, Isfahan (Khorasgan) Branch, Isfahan, Iran
| | | | | | - Morteza Banakar
- Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Moslem Karimzadeh
- Faculty of dentistry, Islamic Azad University, Tehran Medical Sciences, Tehran, Iran
| | - Amirhossein Fathi
- Department of Prosthodontics, Dental Materials Research Center, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.
| |
Collapse
|
|
12
|
Jo SY, Cho HJ, Kim TM. Fenoldopam Mesylate Enhances the Survival of Mesenchymal Stem Cells Under Oxidative Stress and Increases the Therapeutic Function in Acute Kidney Injury. Cell Transplant 2023; 32:9636897221147920. [PMID: 36594258 PMCID: PMC9830573 DOI: 10.1177/09636897221147920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Mesenchymal stem cells (MSCs) have gained interest as an alternative therapeutic option for renal diseases, including acute kidney injury (AKI). However, their use is often limited owing to low survival rates in vivo. Fenoldopam mesylate (FD) is a selective dopamine D1 receptor agonist with antioxidative and anti-apoptotic roles. Herein, we investigated whether FD can enhance the survival of MSCs undergoing oxidative stress in vitro. In addition, the therapeutic effect of MSCs and FD-treated MSCs (FD-MSCs) was compared in a mouse model of AKI induced by cisplatin. The survival of MSCs under oxidative stress was augmented by FD treatment. FD induced the phosphorylation of cAMP response element-binding protein and AKT, contributing to enhanced growth compared with untreated MSCs. The expression of nuclear factor erythroid-2-related factor 2 (NRF2) and heme oxygenase-1 was increased by FD treatment, and nuclear translocation of NRF2 was found exclusively in FD-MSCs. FD downregulated BAX expression, increased the mitochondrial membrane potential, reduced reactive oxygen species generation, and decreased the apoptotic death of MSCs induced by oxidative stress. Moreover, renal function and tubular injury were improved in FD-MSCs compared with non-treated MSCs. Furthermore, tubular injury, apoptosis, and macrophage infiltration, as well as the serum level of tumor necrosis factor-α were reduced, while tubular cell proliferation was markedly increased in FD-MSCs compared with MSCs. Our study demonstrated that FD increases the survivability of MSCs in an oxidative environment, and its use may be effective in preparing robust therapeutic MSCs.
Collapse
Affiliation(s)
- Seo Yeon Jo
- Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang, South Korea
| | - Hye Jin Cho
- Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang, South Korea
| | - Tae Min Kim
- Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang, South Korea,Institutes of Green Bio Science & Technology, Seoul National University, Pyeongchang, South Korea,Tae Min Kim, Graduate School of International Agricultural Technology and Institutes of Green Bio Science & Technology, Seoul National University, Pyeongchang Daero 1447, Pyeongchang 25354, Gangwon-do, South Korea.
| |
Collapse
|
|
13
|
Najafi-Ghalehlou N, Feizkhah A, Mobayen M, Pourmohammadi-Bejarpasi Z, Shekarchi S, Roushandeh AM, Roudkenar MH. Plumping up a Cushion of Human Biowaste in Regenerative Medicine: Novel Insights into a State-of-the-Art Reserve Arsenal. Stem Cell Rev Rep 2022; 18:2709-2739. [PMID: 35505177 PMCID: PMC9064122 DOI: 10.1007/s12015-022-10383-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/25/2022] [Indexed: 12/03/2022]
Abstract
Major breakthroughs and disruptive methods in disease treatment today owe their thanks to our inch by inch developing conception of the infinitive aspects of medicine since the very beginning, among which, the role of the regenerative medicine can on no account be denied, a branch of medicine dedicated to either repairing or replacing the injured or diseased cells, organs, and tissues. A novel means to accomplish such a quest is what is being called "medical biowaste", a large assortment of biological samples produced during a surgery session or as a result of physiological conditions and biological activities. The current paper accentuating several of a number of promising sources of biowaste together with their plausible applications in routine clinical practices and the confronting challenges aims at inspiring research on the existing gap between clinical and basic science to further extend our knowledge and understanding concerning the potential applications of medical biowaste.
Collapse
Affiliation(s)
- Nima Najafi-Ghalehlou
- Department of Medical Laboratory Sciences, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Feizkhah
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammadreza Mobayen
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Zahra Pourmohammadi-Bejarpasi
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Shima Shekarchi
- Anatomical Sciences Department, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Amaneh Mohammadi Roushandeh
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
| | - Mehryar Habibi Roudkenar
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
- Cardiovascular Diseases Research Center, Department of Cardiology, School of Medicine, Heshmat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
| |
Collapse
|
|
14
|
Regenerative and Anti-Inflammatory Potential of Regularly Fed, Starved Cells and Extracellular Vesicles In Vivo. Cells 2022; 11:cells11172696. [PMID: 36078106 PMCID: PMC9455002 DOI: 10.3390/cells11172696] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/20/2022] [Accepted: 08/25/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Mesenchymal stem/stromal cells (MSC) have been employed successfully in immunotherapy and regenerative medicine, but their therapeutic potential is reduced considerably by the ischemic environment that exists after transplantation. The assumption that preconditioning MSC to promote quiescence may result in increased survival and regenerative potential upon transplantation is gaining popularity. Methods: The purpose of this work was to evaluate the anti-inflammatory and regenerative effects of human bone marrow MSC (hBM-MSC) and their extracellular vesicles (EVs) grown and isolated in a serum-free medium, as compared to starved hBM-MSC (preconditioned) in streptozotocin-induced diabetic fractured male C57BL/6J mice. Results: Blood samples taken four hours and five days after injection revealed that cells, whether starved or not, generated similar plasma levels of inflammatory-related cytokines but lower levels than animals treated with EVs. Nonetheless, starved cells prompted the highest production of IL-17, IL-6, IL-13, eotaxin and keratinocyte-derived chemokines and induced an earlier soft callus formation and mineralization of the fracture site compared to EVs and regularly fed cells five days after administration. Conclusions: Preconditioning may be crucial for refining and defining new criteria for future MSC therapies. Additionally, the elucidation of mechanisms underpinning an MSC’s survival/adaptive processes may result in increased cell survival and enhanced therapeutic efficacy following transplantation.
Collapse
|
|
15
|
Goodarzi A, Valikhani M, Amiri F, Safari A. The mechanisms of mutual relationship between malignant hematologic cells and mesenchymal stem cells: Does it contradict the nursing role of mesenchymal stem cells? Cell Commun Signal 2022; 20:21. [PMID: 35236376 PMCID: PMC8889655 DOI: 10.1186/s12964-022-00822-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 12/18/2021] [Indexed: 12/15/2022] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) are known as the issue in biology because of some unpredictable characteristics in the different microenvironments especially in their bone marrow niche. MSCs are used in the regenerative medicine because of their unique potentials for trans-differentiation, immunomodulation, and paracrine capacity. But, their pathogenic and pro-survival effects in tumors/cancers including hematologic malignancies are indisputable. MSCs and/or their derivatives might be involved in tumor growth, metastasis and drug resistance in the leukemias. One of important relationship is MSCs and hematologic malignancy-derived cells which affects markedly the outcome of disease. The communication between these two cells may be contact-dependent and/or contact-independent. In this review, we studied the crosstalk between MSCs and malignant hematologic cells which results the final feedback either the progression or suppression of blood cell malignancy. Video abstract.
Collapse
Affiliation(s)
- Alireza Goodarzi
- Department of Medical Laboratory Sciences, School of Paramedicine, Hamadan University of Medical Sciences, Shahid Fahmideh Blvd., The Opposite Side of Mardom Park, Hamadan, 6517838741, Iran
| | - Mohsen Valikhani
- Hematology Department, School of Allied Medical Science, Iran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Amiri
- Department of Medical Laboratory Sciences, School of Paramedicine, Hamadan University of Medical Sciences, Shahid Fahmideh Blvd., The Opposite Side of Mardom Park, Hamadan, 6517838741, Iran.
| | - Armita Safari
- Student Research Committee, Hamadan University of Medical Science, Hamadan, Iran
| |
Collapse
|
|
16
|
Pang QM, Chen SY, Fu SP, Zhou H, Zhang Q, Ao J, Luo XP, Zhang T. Regulatory Role of Mesenchymal Stem Cells on Secondary Inflammation in Spinal Cord Injury. J Inflamm Res 2022; 15:573-593. [PMID: 35115806 PMCID: PMC8802142 DOI: 10.2147/jir.s349572] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 12/24/2021] [Indexed: 12/13/2022] Open
Affiliation(s)
- Qi-Ming Pang
- Key Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine Centre, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China
- Department of Orthopedics, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China
| | - Si-Yu Chen
- Key Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine Centre, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China
| | - Sheng-Ping Fu
- Key Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine Centre, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China
- Department of Orthopedics, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China
| | - Hui Zhou
- The First School of Clinical Medicine, Zunyi Medical University, Zunyi, People’s Republic of China
| | - Qian Zhang
- Department of Human Anatomy, Zunyi Medical University, Zunyi, People’s Republic of China
| | - Jun Ao
- Department of Orthopedics, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China
| | - Xiao-Ping Luo
- Key Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine Centre, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China
| | - Tao Zhang
- Key Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine Centre, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China
- Department of Orthopedics, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China
- Correspondence: Tao Zhang; Qian Zhang, Email ;
| |
Collapse
|
|
17
|
Alshareef GH, Mohammed AE, Abumaree M, Basmaeil YS. Phenotypic and Functional Responses of Human Decidua Basalis Mesenchymal Stem/Stromal Cells to Lipopolysaccharide of Gram-Negative Bacteria. STEM CELLS AND CLONING-ADVANCES AND APPLICATIONS 2021; 14:51-69. [PMID: 34754198 PMCID: PMC8572118 DOI: 10.2147/sccaa.s332952] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 10/11/2021] [Indexed: 12/24/2022]
Abstract
Introduction Human decidua basalis mesenchymal stem cells (DBMSCs) are potential therapeutics for the medication to cure inflammatory diseases, like atherosclerosis. The current study investigates the capacity of DBMSCs to stay alive and function in a harmful inflammatory environment induced by high levels of lipopolysaccharide (LPS). Methods DBMSCs were exposed to different levels of LPS, and their viability and functional responses (proliferation, adhesion, and migration) were examined. Furthermore, DBMSCs’ expression of 84 genes associated with their functional activities in the presence of LPS was investigated. Results Results indicated that LPS had no significant effect on DBMSCs’ adhesion, migration, and proliferation (24 h and 72 h) (p > 0.05). However, DBMSCs’ proliferation was significantly reduced at 10 µg/mL of LPS at 48 h (p < 0.05). In addition, inflammatory cytokines and receptors related to adhesion, proliferation, migration, and differentiation were significantly overexpressed when DBMSCs were treated with 10 µg/mL of LPS (p < 0.05). Conclusion These results indicated that DBMSCs maintained their functional activities (proliferation, adhesion, and migration) in the presence of LPS as there was no variation between the treated DBMSCs and the control group. This study will lay the foundation for future preclinical and clinical studies to confirm the appropriateness of DBMSCs as a potential medication to cure inflammatory diseases, like atherosclerosis.
Collapse
Affiliation(s)
- Ghofran Hasan Alshareef
- Biology Department, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, 84428, Saudi Arabia
| | - Afrah E Mohammed
- Biology Department, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, 84428, Saudi Arabia
| | - Mohammed Abumaree
- Stem Cell & Regenerative Medicine Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.,College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, 11481, Saudi Arabia
| | - Yasser S Basmaeil
- Stem Cell & Regenerative Medicine Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| |
Collapse
|
|
18
|
Dunbar H, Weiss DJ, Rolandsson Enes S, Laffey JG, English K. The Inflammatory Lung Microenvironment; a Key Mediator in MSC Licensing. Cells 2021; 10:cells10112982. [PMID: 34831203 PMCID: PMC8616504 DOI: 10.3390/cells10112982] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 10/28/2021] [Accepted: 10/29/2021] [Indexed: 12/12/2022] Open
Abstract
Recent clinical trials of mesenchymal stromal cell (MSC) therapy for various inflammatory conditions have highlighted the significant benefit to patients who respond to MSC administration. Thus, there is strong interest in investigating MSC therapy in acute inflammatory lung conditions, such as acute respiratory distress syndrome (ARDS). Unfortunately, not all patients respond, and evidence now suggests that the differential disease microenvironment present across patients and sub-phenotypes of disease or across disease severities influences MSC licensing, function and therapeutic efficacy. Here, we discuss the importance of licensing MSCs and the need to better understand how the disease microenvironment influences MSC activation and therapeutic actions, in addition to the need for a patient-stratification approach.
Collapse
Affiliation(s)
- Hazel Dunbar
- Department of Biology, Maynooth University, W23 F2H6 Maynooth, Ireland;
- Kathleen Lonsdale Institute for Human Health Research, Maynooth University, W23 F2H6 Maynooth, Ireland
| | - Daniel J Weiss
- Department of Medicine, 226 Health Science Research Facility, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA;
| | - Sara Rolandsson Enes
- Department of Experimental Medical Science, Faculty of Medicine, Lund University, 22100 Lund, Sweden;
| | - John G Laffey
- Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland Galway, H91 W2TY Galway, Ireland;
- Department of Anaesthesia, Galway University Hospitals, SAOLTA University Health Group, H91 YR71 Galway, Ireland
| | - Karen English
- Department of Biology, Maynooth University, W23 F2H6 Maynooth, Ireland;
- Kathleen Lonsdale Institute for Human Health Research, Maynooth University, W23 F2H6 Maynooth, Ireland
- Correspondence: ; Tel.: +353-1-7086290
| |
Collapse
|
|
19
|
Tsubosaka M, Maruyama M, Huang EE, Zhang N, Utsunomiya T, Gao Q, Shen H, Li X, Kushioka J, Hirata H, Yao Z, Yang YP, Goodman SB. Effect on Osteogenic Differentiation of Genetically Modified IL4 or PDGF-BB Over-Expressing and IL4-PDGF-BB Co-Over-Expressing Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro. Bioengineering (Basel) 2021; 8:bioengineering8110165. [PMID: 34821731 PMCID: PMC8614682 DOI: 10.3390/bioengineering8110165] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 10/25/2021] [Accepted: 10/28/2021] [Indexed: 11/25/2022] Open
Abstract
The use of genetically modified (GM) mesenchymal stromal cells (MSCs) and preconditioned MSCs (pMSCs) may provide further opportunities to improve the outcome of core decompression (CD) for the treatment of early-stage osteonecrosis of the femoral head (ONFH). GM interleukin-4 (IL4) over-expressing MSCs (IL4-MSCs), platelet-derived growth factor (PDGF)-BB over-expressing MSCs (PDGF-BB-MSCs), and IL4-PDGF-BB co-over-expressing MSCs (IL4-PDGF-BB-MSCs) and their respective pMSCs were used in this in vitro study and compared with respect to cell proliferation and osteogenic differentiation. IL4-MSCs, PDGF-BB-MSCs, IL4-PDGF-BB-MSCs, and each pMSC treatment significantly increased cell proliferation compared to the MSC group alone. The percentage of Alizarin red-stained area in the IL4-MSC and IL4-pMSC groups was significantly lower than in the MSC group. However, the percentage of Alizarin red-stained area in the PDGF-BB-MSC group was significantly higher than in the MSC and PDGF-BB-pMSC groups. The percentage of Alizarin red-stained area in the IL4-PDGF-BB-pMSC was significantly higher than in the IL4-PDGF-BB-MSC group. There were no significant differences in the percentage of Alizarin red-stained area between the MSC and IL4-PDGF-BB-pMSC groups. The use of PDGF-BB-MSCs or IL4-PDGF-BB-pMSCs increased cell proliferation. Furthermore, PDGF-BB-MSCs promoted osteogenic differentiation. The addition of GM MSCs may provide a useful supplementary cell-based therapy to CD for treatment of ONFH.
Collapse
Affiliation(s)
- Masanori Tsubosaka
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
| | - Masahiro Maruyama
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
| | - Elijah Ejun Huang
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
| | - Ning Zhang
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
| | - Takeshi Utsunomiya
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
| | - Qi Gao
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
| | - Huaishuang Shen
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
| | - Xueping Li
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
| | - Junichi Kushioka
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
| | - Hirohito Hirata
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
| | - Zhenyu Yao
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
| | - Yunzhi Peter Yang
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
- Department of Material Science and Engineering, Stanford University School of Medicine, Stanford, CA 94305, USA
- Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Stuart B. Goodman
- Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA 94063, USA; (M.T.); (M.M.); (E.E.H.); (N.Z.); (T.U.); (Q.G.); (H.S.); (X.L.); (J.K.); (H.H.); (Z.Y.); (Y.P.Y.)
- Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA
- Correspondence: ; Tel.: +1-650-498-4343
| |
Collapse
|
|
20
|
Pourmohammadi-Bejarpasi Z, Sabzevari R, Mohammadi Roushandeh A, Ebrahimi A, Mobayen M, Jahanian-Najafabadi A, Darjani A, Habibi Roudkenar M. Combination Therapy of Metadichol Nanogel and Lipocalin-2 Engineered Mesenchymal Stem Cells Improve Wound Healing in Rat Model of Excision Injury. Adv Pharm Bull 2021; 12:550-560. [PMID: 35935055 PMCID: PMC9348536 DOI: 10.34172/apb.2022.059] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 05/29/2021] [Accepted: 09/11/2021] [Indexed: 11/11/2022] Open
Abstract
Purpose: Currently, several disorders including burns, trauma, excisional and diabetic wounds, and bedsores threaten the human health. Application of mesenchymal stem cells (MSCs) is recommended for treatment of skin disorders. However, because of oxidative stress and inflammation after skin injury, survival of transplanted MSCs is low which in turn negatively affects the efficiency of the MSCs-based therapy. In an attempt to address the aforementioned challenge and introducing a novel potential therapeutic strategy, we employed combination therapy by lipocalin 2 (Lcn2)-engineered MSCs and a Metadichol (an inverse agonist of vitamin D receptor (VDR)) nanogel in a rat model of excisional wound.
Methods: First, human umbilical cord MSCs (hUC-MSCs) was transfected by a recombinant plasmid encoding Lcn2 gene. Next, a combination of Metadichol nanogel and the engineered MSCs was co-applied on wound in rat model of excision injury. Finally the improvement of wound healing in experimental groups was evaluated by photography and histological assessments (hematoxylin and eosin staining).
Results: Our findings revealed that the repair rate was higher in the group received combination therapy comparing to control groups. Notably, Metadichol+Lcn2-MSCs showed significantly higher wound contraction rate compared to control group at all time points (P value < 0.001). Furthermore, wound repair rate was 95% 14 days after surgery, and 100% after 21 days in the treatment groups. Our results also revealed that the combination therapy improved and accelerated the wound healing process.
Conclusion: Our findings suggest a novel potential therapeutic strategy i.e. Lcn2-engineered MSCs and Metadichol for wound healing. However, further preclinical and clinical studies are required.
Collapse
Affiliation(s)
| | - Reza Sabzevari
- Medical Biotechnology Department, Paramedicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
| | - Amaneh Mohammadi Roushandeh
- Cellular and Molecular Research Center, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
- Burn and Regenerative Research Center, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
| | - Ammar Ebrahimi
- Medical Biotechnology Department, Paramedicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammadreza Mobayen
- Burn and Regenerative Research Center, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
| | - Ali Jahanian-Najafabadi
- Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
| | - Abbas Darjani
- Skin Research Center, Department of Dermatology, Razi Hospital, School of Medicine, Guilan University of Medical Science, Rasht, Iran
| | - Mehryar Habibi Roudkenar
- Cellular and Molecular Research Center, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
- Burn and Regenerative Research Center, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
| |
Collapse
|
|
21
|
Shekarchi S, Roushandeh AM, Roudkenar MH, Bahadori MH. Dimethyl fumarate prevents cytotoxicity and apoptosis mediated by oxidative stress in human adipose-derived mesenchymal stem cells. Mol Biol Rep 2021; 48:6375-6385. [PMID: 34426902 DOI: 10.1007/s11033-021-06638-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 08/10/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND The poor survival rate and undesirable homing of transplanted stem cells are the major challenges in stem cell therapy. Addressing the challenge would improve the therapeutic efficacy of these cells. Dimethyl fumarate (DMF) is an anti-inflammatory drug that exerts its effects through the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Therefore, its cytoprotective effects on human adipose-derived MSCs (hASCs) against various oxidative stresses have been investigated in this study. METHODS AND RESULTS hASCs were cultured with different concentrations of DMF to evaluate the cytotoxicity of DMF on hASCs using Cell Counting Kit-8 (CCK-8). Besides, the migration ability of the cells after DMF treatment was evaluated using the Transwell method. Furthermore, the expression of HO-1 and NQO-1 was determined using RT-PCR. The cytoprotective effects of DMF on hASCs against the oxidative stress caused by H2O2 and Ultra Violet (UV) were evaluated by assessing cell proliferation and apoptosis. Our results demonstrated that under oxidative stress conditions induced by H2O2 and UV, DMF increased the survival rate and proliferation of the cells and prevented apoptosis. Moreover, the expression of HO-1 and NQO-1 was upregulated in hASCs pretreated with DMF which confirms the activation of the Nrf2 pathway. However, DMF significantly decreased migration in hADSCs (P < 0.0001). CONCLUSION Our findings indicate that DMF enhances the proliferation capability and viability of hASCs and prevents their apoptosis in harsh stressful microenvironments. However, the applicability of DMF as a cytoprotective factor for the augmentation of hASCs requires in-depth preclinical and clinical studies.
Collapse
Affiliation(s)
- Shima Shekarchi
- Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Amaneh Mohammadi Roushandeh
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
| | - Mehryar Habibi Roudkenar
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammad Hadi Bahadori
- Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
| |
Collapse
|
|
22
|
Alijani-Ghazyani Z, Sabzevari R, Roushandeh AM, Jahanian-Najafabadi A, Amiri F, Roudkenar MH. Transplantation of Umbilical Cord-Derived Mesenchymal Stem Cells Overexpressing Lipocalin 2 Ameliorates Ischemia-Induced Injury and Reduces Apoptotic Death in a Rat Acute Myocardial Infarction Model. Stem Cell Rev Rep 2021; 16:968-978. [PMID: 32656623 DOI: 10.1007/s12015-020-10007-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Myocardial infarction (MI) is a leading cause of death worldwide and requires development of efficient therapeutic strategies . Mesenchymal stem cells (MSCs) -based therapy of MI has been promising but inefficient due to undesirable microenvironment of the infarct tissue. Hence, the current study was conducted to fortify MSCs against the unfavorable microenvironment of infarct tissue via overexpression of Lipocalin 2 (Lcn2) as a cytoprotective factor. The engineered cells (Lcn2-MSCs) were transplanted to infarcted heart of a rat model of MI. According to our findings, Lcn2 overexpression resulted in increased MSCs survival in the MI tissue (p < 0.05) compared to non-engineered cells. Furthermore, the infusion of Lcn2-MSCs mitigated Left ventricle (LV) remodeling, decreased fibrosis (p < 0.0001), and reduced apoptotic death of the LVs' cells (p < 0.0001) compared to the control. Our findings suggest a potential novel therapeutic strategy for MI, however, further investigations such as safety and efficacy assessments in large animals followed by clinical trials are required.
Collapse
Affiliation(s)
- Zahra Alijani-Ghazyani
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Reza Sabzevari
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Amaneh Mohammadi Roushandeh
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran.,Anatomical Sciences Department, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
| | - Ali Jahanian-Najafabadi
- Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fatemeh Amiri
- Department of Medical Laboratory Science, Paramedicine Faculty, Hamadan University of Medical Science, Hamadan, Iran
| | - Mehryar Habibi Roudkenar
- Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
| |
Collapse
|
|
23
|
Anti-apoptotic effect of Nisin as a prebiotic on human mesenchymal stem cells in harsh condition. Cell Tissue Bank 2021; 23:227-236. [PMID: 34043109 DOI: 10.1007/s10561-021-09933-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 04/24/2021] [Indexed: 10/21/2022]
Abstract
Mesenchymal stem cells (MSCs) are progenitor cells of connective tissue with the ability of proliferation, self-renewal, and multilineage differentiation that make it a promising source with an enormous potential to be utilized for tissue repairing and vehicles of cell-based gene therapy. The low survival rate of MSCs following transplantation is their drawback. Preconditioning with some factors is a novel and effective strategy, improving the survival of the cells by protecting them from harmful conditions and result in the good recovery of injured tissues. Nisin is a prebiotic with antimicrobial activity. This manuscript aimed to evaluate the effect of Nisin preconditioning of MSCs on in vitro cell viability. MSCs were cultured and preconditioned with Nisin in different concentrations. Then, they are separately exposed to H2O2 and serum deprivation. Cell survival and cell apoptosis were evaluated by MTT assay and Real-time PCR, respectively. Furthermore, Annexin-PI staining and caspase activity was performed to visualize apoptotic cells. MSC-Nisin viability and proliferation significantly increased when exposed to H2O2 and serum deprivation, compared to that of MSCs. About 250 and 500 IU/mL of Nisin donate a significant anti-apoptotic impact to MSCs. Our data suggest that preconditioning with Nisin has been improved cell viability and the anti-apoptotic capacity of MSCs. However, the mechanism related to the protective properties of preconditioning and using this strategy in stem cell therapy requires more research.
Collapse
|
|
24
|
Gorodetsky R, Aicher WK. Allogenic Use of Human Placenta-Derived Stromal Cells as a Highly Active Subtype of Mesenchymal Stromal Cells for Cell-Based Therapies. Int J Mol Sci 2021; 22:5302. [PMID: 34069909 PMCID: PMC8157571 DOI: 10.3390/ijms22105302] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/14/2021] [Accepted: 05/14/2021] [Indexed: 12/13/2022] Open
Abstract
The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow (BM, bmMSCs), adipose tissue (atMSCs), and human term placenta (hPSCs) has been proposed for various clinical purposes. Accumulated evidence suggests that the activity of the different MSCs is indirect and associated with paracrine release of pro-regenerative and anti-inflammatory factors. A major limitation of bmMSCs-based treatment for autologous application is the limited yield of cells harvested from BM and the invasiveness of the procedure. Similar effects of autologous and allogeneic MSCs isolated from various other tissues were reported. The easily available fresh human placenta seems to represent a preferred source for harvesting abundant numbers of human hPSCs for allogenic use. Cells derived from the neonate tissues of the placenta (f-hPSC) can undergo extended expansion with a low risk of senescence. The low expression of HLA class I and II on f-hPSCs reduces the risk of rejection in allogeneic or xenogeneic applications in normal immunocompetent hosts. The main advantage of hPSCs-based therapies seems to lie in the secretion of a wide range of pro-regenerative and anti-inflammatory factors. This renders hPSCs as a very competent cell for therapy in humans or animal models. This review summarizes the therapeutic potential of allogeneic applications of f-hPSCs, with reference to their indirect pro-regenerative and anti-inflammatory effects and discusses clinical feasibility studies.
Collapse
Affiliation(s)
- Raphael Gorodetsky
- Biotechnology and Radiobiology Laboratory, Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
| | - Wilhelm K. Aicher
- Center of Medical Research, Department of Urology at UKT, Eberhard-Karls-University, 72076 Tuebingen, Germany
| |
Collapse
|
|
25
|
Exosomes derived from miR-1228 overexpressing bone marrow-mesenchymal stem cells promote growth of gastric cancer cells. Aging (Albany NY) 2021; 13:11808-11821. [PMID: 33883305 PMCID: PMC8109060 DOI: 10.18632/aging.202878] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 10/27/2020] [Indexed: 01/23/2023]
Abstract
There has been increasing evidence that microRNAs (miRNAs) are related to glioma progression, and that genetically engineered mesenchymal stem cells (MSCs) can inhibit the growth of gliomas. However, the underlying mechanism of bone marrow-MSCs (BM--MSCs) and miRs in gastric cancer still remains unclear. Patients with gastric cancer treated in Shijiazhuang First Hospital as well as healthy individuals undergoing physical examinations were recruited to measure the expression of exosomal miR-1228. Receiver operating characteristic (ROC) curves were plotted and the patients were followed up. BM--MSCs from healthy subjects were collected and exosomes were extracted. The MSC cells were transfected with lentiviral vectors carrying miR-1228 and MMP-14 over-expression sequences and scramble sequence, followed by exosome extraction. The exosomes were co-cultured with SGC-7901 and MGC-823 cells to detect cell proliferation, invasion, apoptosis and migration. The correlation between miR-1228 and MMP-14 was determined by dual-luciferase reporter assay. miR-1228 was highly expressed in serum exosomes of patients with gastric cancer with a area under ROC curve (AUC) of 0.865. The exosomes derived from BM-MSCs are expected to be efficient nanocarriers. Up-regulation of miR-1228 can down-regulate the expression of MMP-14 and effectively hinders the development and progression of gastric cancer.
Collapse
|
|
26
|
Dutta SD, Patel DK, Jin B, Choi SI, Lee OH, Lim KT. Effects of Cirsium setidens (Dunn) Nakai on the osteogenic differentiation of stem cells. Mol Med Rep 2021; 23:264. [PMID: 33576449 PMCID: PMC7893721 DOI: 10.3892/mmr.2021.11903] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 11/02/2020] [Indexed: 12/15/2022] Open
Abstract
Cirsium setidens (Dunn) Nakai, commonly known as gondre, is a perennial herb that grows predominantly in South Korea. It contains several bioactive phytochemicals with antioxidant, anti-cancer, anti-tumor and anti-inflammatory properties. The present study aimed to investigate the effects of methanolic extracts of gondre on osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). As characterized by nuclear magnetic resonance spectroscopy and matrix-assisted laser deposition/ionization (time-of-flight) mass spectrometry, the methanol extract of gondre was found to be enriched with pectolinarin. After 48 h, enhanced viability of hPDLSCs was observed in the presence of gondre compared with under control conditions, suggesting the biocompatibility of gondre. Notably, biocompatibility was markedly affected by gondre concentration in cultured media. Relatively high cell viability was observed in medium containing 0.05% gondre. Furthermore, mineralization was significantly higher in hPDLSCs in the presence of gondre compared with that in control cells, indicating their mineralization potential. Increased expression of various transcription markers, such as collagen 1, runt-related transcription factor 2, bone sialoprotein and alkaline phosphatase, was also detected when hPDLSCs were stimulated with gondre compared with in the control groups, further confirming the superior osteogenic potential of gondre extract for tissue engineering applications, particularly in bone tissues.
Collapse
Affiliation(s)
- Sayan Deb Dutta
- Department of Biosystems Engineering, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea
| | - Dinesh K Patel
- Department of Biosystems Engineering, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea
| | - Bin Jin
- Department of Stomatology, Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, P.R. China
| | - Sun-Il Choi
- Department of Food Science and Biotechnology, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea
| | - Ok Hwan Lee
- Department of Food Science and Biotechnology, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea
| | - Ki-Taek Lim
- Department of Biosystems Engineering, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea
| |
Collapse
|
|
27
|
Effect of Preconditioned Mesenchymal Stem Cells with Nisin Prebiotic on the Expression of Wound Healing Factors Such as TGF-β1, FGF-2, IL-1, IL-6, and IL-10. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2021. [DOI: 10.1007/s40883-021-00194-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
|
|
28
|
Huang D, Siaw-Debrah F, Wang H, Ye S, Wang K, Wu K, Zhang Y, Wang H, Yao C, Chen J, Yan L, Zhang CL, Zhuge Q, Yang J. Transplanting Rac1-silenced bone marrow mesenchymal stem cells promote neurological function recovery in TBI mice. Aging (Albany NY) 2020; 13:2822-2850. [PMID: 33411679 PMCID: PMC7880331 DOI: 10.18632/aging.202334] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 11/18/2020] [Indexed: 12/02/2022]
Abstract
Bone marrow mesenchymal stem cells (BMMSCs)-based therapy has emerged as a promising novel therapy for Traumatic Brain Injury (TBI). However, the therapeutic quantity of viable implanted BMMSCs necessary to initiate efficacy is still undetermined. Increased oxidative stress following TBI, which leads to the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase signaling pathway, has been implicated in accounting for the diminished graft survival and therapeutic effect. To prove this assertion, we silenced the expression of NADPH subunits (p22-phox, p47-phox, and p67-phox) and small GTPase Rac1 in BMMSCs using shRNA. Our results showed that silencing these proteins significantly reduced oxidative stress and cell death/apoptosis, and promoted implanted BMMSCs proliferation after TBI. The most significant result was however seen with Rac1 silencing, which demonstrated decreased expression of apoptotic proteins, enhanced in vitro survival ratio, reduction in TBI lesional volume and significant improvement in neurological function post shRac1-BMMSCs transplantation. Additionally, two RNA-seq hub genes (VEGFA and MMP-2) were identified to play critical roles in shRac1-mediated cell survival. In summary, we propose that knockdown of Rac1 gene could significantly boost cell survival and promote the recovery of neurological functions after BMMSCs transplantation in TBI mice.
Collapse
Affiliation(s)
- Dongdong Huang
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Felix Siaw-Debrah
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Hua Wang
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Sheng Ye
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Kankai Wang
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Ke Wu
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Ying Zhang
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Hao Wang
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Chaojie Yao
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Jiayu Chen
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Lin Yan
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Chun-Li Zhang
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
| | - Qichuan Zhuge
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Jianjing Yang
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| |
Collapse
|
|
29
|
Hydrogen Peroxide-Preconditioned Human Adipose-Derived Stem Cells Enhance the Recovery of Oligodendrocyte-Like Cells after Oxidative Stress-Induced Damage. Int J Mol Sci 2020; 21:ijms21249513. [PMID: 33327653 PMCID: PMC7765141 DOI: 10.3390/ijms21249513] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 12/11/2020] [Accepted: 12/12/2020] [Indexed: 12/17/2022] Open
Abstract
Oxidative stress associated with neuroinflammation is a key process involved in the pathophysiology of neurodegenerative diseases, and therefore, has been proposed as a crucial target for new therapies. Recently, the therapeutic potential of human adipose-derived stem cells (hASCs) has been investigated as a novel strategy for neuroprotection. These cells can be preconditioned by exposing them to mild stress in order to improve their response to oxidative stress. In this study, we evaluate the therapeutic potential of hASCs preconditioned with low doses of H2O2 (called HC016 cells) to overcome the deleterious effect of oxidative stress in an in vitro model of oligodendrocyte-like cells (HOGd), through two strategies: i, the culture of oxidized HOGd with HC016 cell-conditioned medium (CM), and ii, the indirect co-culture of oxidized HOGd with HC016 cells, which had or had not been exposed to oxidative stress. The results demonstrated that both strategies had reparative effects, oxidized HC016 cell co-culture being the one associated with the greatest recovery of the damaged HOGd, increasing their viability, reducing their intracellular reactive oxygen species levels and promoting their antioxidant capacity. Taken together, these findings support the view that HC016 cells, given their reparative capacity, might be considered an important breakthrough in cell-based therapies.
Collapse
|
|
30
|
Alijani-Ghazyani Z, Roushandeh AM, Sabzevari R, Salari A, Razavi Toosi MT, Jahanian-Najafabadi A, Roudkenar MH. Conditioned medium harvested from Hif1α engineered mesenchymal stem cells ameliorates LAD-occlusion -induced injury in rat acute myocardial ischemia model. Int J Biochem Cell Biol 2020; 130:105897. [PMID: 33279679 DOI: 10.1016/j.biocel.2020.105897] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 11/25/2020] [Accepted: 11/26/2020] [Indexed: 12/31/2022]
Abstract
Acute myocardial infarction (AMI) is the most common type of ischemic heart diseases with a high mortality rate. Although recent advances in medical cares and therapies have increased the patient's outcomes, but, still there is no real and effective therapeutic modality for AMI. Hence, development of novel therapeutic strategies is under focus of investigations. MSCs-based therapy has been proposed for AMI, though its efficacy is controversial yet. It is believed that MSCs exert their healing effects via secretion of growth factors/cytokines. However, these cells produce a very minute amount of the factors under normal cultivation. Here, in an attempt to improve the potential therapeutic effect of MSCs-derived conditioned medium (CM) on AMI, we transfected the cells with a recombinant plasmid encoding Hif1α-3A (a mutant form of Hif1α stable under normoxic condition), so Hif1α expression and secretion into CM (MSCs-Hif1α-CM) could be up-regulated under normoxic condition. The therapeutic potential of the MSCs-Hif1α-3A-CM was investigated in a rat model of AMI and compared to the CM harvested from non-manipulated MSCs. Our results showed that the MSCs-Hif1α-3A-CM mitigated MI-induced tissues injury, decreased fibrosis, reduced apoptosis, and limited infarct area size. These findings propose a potential therapeutic strategy for treatment of AMI. However, further preclinical and clinical investigations in this regard are still needed.
Collapse
Affiliation(s)
- Zahra Alijani-Ghazyani
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Amaneh Mohammadi Roushandeh
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran; Anatomical Sciences Department, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
| | - Reza Sabzevari
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Arsalan Salari
- Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammad Taghi Razavi Toosi
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Ali Jahanian-Najafabadi
- Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehryar Habibi Roudkenar
- Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
| |
Collapse
|
|
31
|
Fazal N, Khawaja H, Naseer N, Khan AJ, Latief N. Daphne mucronata enhances cell proliferation and protects human adipose stem cells against monosodium iodoacetate induced oxidative stress in vitro. Adipocyte 2020; 9:495-508. [PMID: 32867575 PMCID: PMC7714443 DOI: 10.1080/21623945.2020.1812242] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/11/2020] [Accepted: 08/15/2020] [Indexed: 01/01/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are being used to treat many diseases as they exhibit great regenerative potential. However, MSC's transplantation sometimes does not yield the maximum regenerative outcome as they are unable to survive in inflammatory conditions. Several approaches including preconditioning are used to improve the survival rate of mesenchymal stem cells. One such recently reported approach is preconditioning MSCs with plant extracts. The present study was designed to evaluate the effect of Daphne mucronata extract on stressed human adipose-derived mesenchymal stem cells (hADMSCs). Isolated hADMSCs were preconditioned with different concentrations of Daphne muconata extract and the protective, proliferative, antioxidant and anti-inflammatory effect was assessed through various assays and expression analysis of inflammatory markers regulated through NF-κB pathway. Results suggest that preconditioning hADMSCs with Daphne mucronata increased the cell viability, proliferative and protective potential of hADMSCs with a concomitant reduction in LDH, ROS and elevation in SOD activity. Moreover, both the ELISA and gene expression analysis demonstrated down regulations of inflammatory markers (IL1-β, TNF-α, p65, p50, MMP13) in Daphne mucronata preconditioned hADMSCs as compared to stress. This is the first study to report the use of MIA induced oxidative stress against hADMSC's and effect of Daphne mucronata on stressed hADMSCs. Results of these studies provided evidence that Daphne mucronata protects the hADMSCs during stress conditions by down regulating the inflammatory markers and hence increase the viability and proliferative potential of hADMSCs that is crucial for transplantation purposes.
Collapse
Affiliation(s)
- Numan Fazal
- National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Hamzah Khawaja
- National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Nadia Naseer
- National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Azim Jahangir Khan
- Allama Iqbal Medical College, University of Health Sciences, Lahore, Pakistan
| | - Noreen Latief
- National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
| |
Collapse
|
|
32
|
Khoshlahni N, Sagha M, Mirzapour T, Zarif MN, Mohammadzadeh-Vardin M. Iron depletion with deferoxamine protects bone marrow-derived mesenchymal stem cells against oxidative stress-induced apoptosis. Cell Stress Chaperones 2020; 25:1059-1069. [PMID: 32729002 PMCID: PMC7591652 DOI: 10.1007/s12192-020-01142-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 07/12/2020] [Accepted: 07/20/2020] [Indexed: 01/11/2023] Open
Abstract
Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent cells with self-renewal properties, making them an ideal candidate for regenerative medicine. Recently, numerous studies show that about more than 99% of transplanted cells are destroyed because of the stressful microenvironment. Meanwhile, in the target organs, iron overload can produce oxidative stress introducing it as the most important stress factor. The present study was aimed at increasing BM-MSCs' viability against oxidative stress microenvironment using iron depletion by deferoxamine (DFO). Mesenchymal stem cells are isolated and characterized from rat bone marrow. Then, the sensitivity of BM-MSCs against H2O2-induced oxidative stress was evaluated through half of the inhibitory concentration (IC50) estimation by using MTT assay. The maximum non-inhibitory concentration of DFO on BM-MSCs was determined. The next step was the comparison between DFO pre-treated BM-MSCs and untreated cells against H2O2-induced apoptosis. BM-MSCs were identified with morphologic and flow cytometry analysis. IC50 of H2O2 was determined as 0.55 mM at 4 h. Also, the maximum non-inhibitory concentration of DFO was ascertained as 5 μM at 48 h. Our results demonstrated that pretreatment with DFO significantly potentiates BM-MSCs against H2O2-induced oxidative stress which was confirmed by MTT assay, AO/EB double staining, DAPI staining, and activated caspase 3 quantification as well as western blot test. Expression of cleaved caspase 3 and pAKT/AKT ratio obviously demonstrated DFO can resist the cells against cytotoxicity. These findings may help to develop better stem cell culture medium for MSC-based cell therapy. Moreover, regulation of cell stress can be used in practical subjects.
Collapse
Affiliation(s)
- Nasrin Khoshlahni
- Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
- Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mohsen Sagha
- Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Tooba Mirzapour
- Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran
| | - Mahin Nikougoftar Zarif
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Mohammad Mohammadzadeh-Vardin
- Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
| |
Collapse
|
|
33
|
Sabzevari R, Roushandeh AM, Mehdipour A, Alini M, Roudkenar MH. SA/G hydrogel containing hCAP-18/LL-37-engineered WJ-MSCs-derived conditioned medium promoted wound healing in rat model of excision injury. Life Sci 2020; 261:118381. [DOI: 10.1016/j.lfs.2020.118381] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 08/18/2020] [Accepted: 08/31/2020] [Indexed: 12/20/2022]
|
|
34
|
Guo L, Du J, Yuan DF, Zhang Y, Zhang S, Zhang HC, Mi JW, Ning YL, Chen MJ, Wen DL, Sun JH, Liu D, Zeng L, Zhang A, Jiang J, Huang H. Optimal H 2O 2 preconditioning to improve bone marrow mesenchymal stem cells' engraftment in wound healing. Stem Cell Res Ther 2020; 11:434. [PMID: 33032649 PMCID: PMC7545926 DOI: 10.1186/s13287-020-01910-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 08/27/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising therapeutic strategy for wound healing. However, the poor migration capacity and low survival rate of transplanted BMSCs in wounds weaken their potential application. OBJECTIVE To identify the optimal protocol for BMSCs preconditioned with H2O2 and improve the therapeutic efficacy using H2O2-preconditioned BMSCs in wound healing. METHODS Mouse BMSCs were exposed to various concentrations of H2O2, and the key cellular functional properties were assessed to determine the optimal precondition with H2O2. The H2O2-preconditioned BMSCs were transplanted into mice with full-thickness excisional wounds to evaluate their healing capacity and tissue engraftment. RESULTS Treatment BMSCs with 50 μM H2O2 for 12 h could significantly enhance their proliferation, migration, and survival by maximizing the upregulation of cyclin D1, SDF-1, and its receptors CXCR4/7 expressions, and activating the PI3K/Akt/mTOR pathway, but inhibiting the expression of p16 and GSK-3β. Meanwhile, oxidative stress-induced BMSC apoptosis was also significantly attenuated by the same protocol pretreatment with a decreased ratio of Bax/Bcl-2 and cleaved caspase-9/3 expression. Moreover, after the identification of the optimal protocol of H2O2 precondition in vitro, the migration and tissue engraftment of transfused BMSCs with H2O2 preconditioning were dramatically increased into the wound site as compared to the un-preconditioned BMSCs. The increased microvessel density and the speedy closure of the wounds were observed after the transfusion of H2O2-preconditioned BMSCs. CONCLUSIONS The findings suggested that 50 μM H2O2 pretreated for 12 h is the optimal precondition for the transplantation of BMSCs, which gives a considerable insight that this protocol may be served as a promising candidate for improving the therapeutic potential of BMSCs for wound healing.
Collapse
Affiliation(s)
- Ling Guo
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Juan Du
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Dan-Feng Yuan
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Ya Zhang
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Shu Zhang
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Hua-Cai Zhang
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Jun-Wei Mi
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Ya-Lei Ning
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Min-Jia Chen
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Da-Lin Wen
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Jian-Hui Sun
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Di Liu
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Ling Zeng
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Anqiang Zhang
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Jianxin Jiang
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Hong Huang
- State Key Laboratory of Trauma, Burns and Combined Injury, Department of Surgical Research, Daping Hospital, Army Medical University, Chongqing, 400042, China.
| |
Collapse
|
|
35
|
Asgarpour K, Shojaei Z, Amiri F, Ai J, Mahjoubin-Tehran M, Ghasemi F, ArefNezhad R, Hamblin MR, Mirzaei H. Exosomal microRNAs derived from mesenchymal stem cells: cell-to-cell messages. Cell Commun Signal 2020; 18:149. [PMID: 32917227 PMCID: PMC7488404 DOI: 10.1186/s12964-020-00650-6] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 08/24/2020] [Indexed: 12/18/2022] Open
Abstract
Exosomes are extracellular vesicles characterized by their size, source, release mechanism and contents. MicroRNAs (miRNAs) are single stranded non-coding RNAs transcribed from DNA. Exosomes and miRNAs are widespread in eukaryotic cells, especially in mesenchymal stem cells (MSCs). MSCs are used for tissue regeneration, and also exert paracrine, anti-inflammatory and immunomodulatory effects. However, the use of MSCs is controversial, especially in the presence or after the remission of a tumor, due to their secretion of growth factors and their migration ability. Instead of intact MSCs, MSC-derived compartments or substances could be used as practical tools for diagnosis, follow up, management and monitoring of diseases. Herein, we discuss some aspects of exosomal miRNAs derived from MSCs in the progression, diagnosis and treatment of various diseases. Video Abstract.
Collapse
Affiliation(s)
- Kasra Asgarpour
- Department of Medicine, University of Western Ontario, London, Ontario, Canada
| | - Zahra Shojaei
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Amiri
- School of Allied Medical Sciences, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Jafar Ai
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine (SATM), Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Maryam Mahjoubin-Tehran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Faezeh Ghasemi
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Reza ArefNezhad
- Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Michael R Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA, 02114, USA.
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, IR, Iran.
| |
Collapse
|
|
36
|
Garrido-Pascual P, Alonso-Varona A, Castro B, Burón M, Palomares T. H 2O 2-preconditioned human adipose-derived stem cells (HC016) increase their resistance to oxidative stress by overexpressing Nrf2 and bioenergetic adaptation. Stem Cell Res Ther 2020; 11:335. [PMID: 32746890 PMCID: PMC7397657 DOI: 10.1186/s13287-020-01851-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 07/17/2020] [Accepted: 07/24/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells, including those derived from human adipose tissue (hASCs), are currently being widely investigated for cell therapy. However, when transplanted at the site of injury, the survival and engraftment rates of hASCs are low, mainly due to the harsh microenvironment they encounter, characterized by inflammation and oxidative stress. To overcome these therapeutic limitations, cell preconditioning with low-concentration of hydrogen peroxide (H2O2) has been proposed as a plausible strategy to increase their survival and adaptation to oxidative stress. Nonetheless, the underlying mechanisms of this approach are not yet fully understood. In this study, we analyzed molecular and bioenergetic changes that take place in H2O2 preconditioned hASCs. METHODS Long-term exposure to a low concentration of H2O2 was applied to obtain preconditioned hASCs (named HC016), and then, their response to oxidative stress was analyzed. The effect of preconditioning on the expression of Nrf2 and its downstream antioxidant enzymes (HO-1, SOD-1, GPx-1, and CAT), and of NF-κB and its related inflammatory proteins (COX-2 and IL-1β), were examined by Western blot. Finally, the Seahorse XF96 Flux analysis system was used to evaluate the mitochondrial respiration and glycolytic function, along with the total ATP production. RESULTS We found that under oxidative conditions, HC016 cells increased the survival by (i) decreasing intracellular ROS levels through the overexpression of the transcription factor Nrf2 and its related antioxidant enzymes HO-1, SOD-1, GPx-1, and CAT; (ii) reducing the secretion of pro-inflammatory molecules COX-2 and IL-1β through the attenuation of the expression of NF-κB; and (iii) increasing the total ATP production rate through the adaption of their metabolism to meet the energetic demand required to survive. CONCLUSIONS H2O2 preconditioning enhances hASC survival under oxidative stress conditions by stimulating their antioxidant response and bioenergetic adaptation. Therefore, this preconditioning strategy might be considered an excellent tool for strengthening the resistance of hASCs to harmful oxidative stress.
Collapse
Affiliation(s)
- Patricia Garrido-Pascual
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.
| | - Ana Alonso-Varona
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain
| | - Begoña Castro
- Histocell, Bizkaia Science and Technology Park, Derio, Bizkaia, Spain
| | - María Burón
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain
| | - Teodoro Palomares
- Department of Surgery, Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain
| |
Collapse
|
|
37
|
Liu Y, Xu L, Hu L, Chen D, Yu L, Li X, Chen H, Zhu J, Chen C, Luo Y, Wang B, Li G. Stearic acid methyl ester promotes migration of mesenchymal stem cells and accelerates cartilage defect repair. J Orthop Translat 2020; 22:81-91. [PMID: 32440503 PMCID: PMC7231966 DOI: 10.1016/j.jot.2019.09.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 08/22/2019] [Accepted: 09/25/2019] [Indexed: 01/07/2023] Open
Abstract
Background Mesenchymal stem cells (MSCs) can be easily expanded without losing the ability of multilineage differentiation, including oesteogenic, chondrogenic and adipogenic differentiation. These characters make MSCs a promising cell resource for cartilage defect repair. MSCs could be recruited by inflammatory stimulation, then home to the injury tissues. However, its capacity of homing is extremely limited. Thus, it has become extremely necessary to develop an agent or a method, which can be used to enhance the efficiency of MSCs homing. This study investigates the effect of stearic acid methyl ester (SAME) on MSCs mobilisation and cartilage regeneration. Methods MSCs were isolated from femurs of Sprague-Dawley (SD) rats. MTT assay was used to detect effect of SAME on viability of MSCs. Transwell assay and wound healing assay were used to detect effect of SAME on migration of MSCs. RNA-seq, quantitative real-time PCR and western blot were performed to analyze the expression of RNAs and proteins. Colony forming assay and flow cytometry were used to evaluate the effect of SAME on MSCs mobilisation in vivo. A rat cartilage defect model was created to evaluate the effect of SAME on cartilage regeneration. Results We found that SAME could promote the migration of MSCs. Interestingly, we found SAME significantly increased the expression levels of Vav1 in MSCs. On the other hand, the enhanced migration ability of MSCs induced by SAME was retarded by Vav1 small interfering RNA (siRNA) and Rho-associated protein kinase 2 (ROCK2) inhibitor. In addition, we also checked the effect of SAME on mobilisation of MSCs in vivo. The results showed that SAME increased the number of MSCs in peripheral blood and enhanced the capacity of colony formation. Finally, using a cartilage defect model in rats, we found SAME could improve cartilage repair. Conclusion Our study demonstrates that SAME can enhance MSCs migration ability mainly through the Vav1/ROCK2 signaling pathway, which could contribute to the accelerated cartilage regeneration. The translational potential of this article These findings provide evidence that SAME could be used as a therapeutic reagent for MSCs mobilisation and cartilage regeneration.
Collapse
Affiliation(s)
- Yamei Liu
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.,The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Liangliang Xu
- Key Laboratory of Orthopaedics & Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.,Laboratory of Orthopaedics & Traumatology, Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Liuchao Hu
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.,Department of Traumatology, The Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510240, China
| | - Dongfeng Chen
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.,The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Lijuan Yu
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.,The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Xican Li
- School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Hongtai Chen
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.,Department of Traumatology, The Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510240, China
| | - Junlang Zhu
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.,Department of Traumatology, The Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510240, China
| | - Chen Chen
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.,The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Yiwen Luo
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.,Department of Traumatology, The Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510240, China
| | - Bin Wang
- School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.,Department of Traumatology, The Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510240, China
| | - Gang Li
- Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.,Stem Cells and Regenerative Medicine Laboratory, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China
| |
Collapse
|
|
38
|
Jin C, Zhou F, Zhang L, Shen J. Overexpression of heat shock protein 70 enhanced mesenchymal stem cell treatment efficacy in phosgene-induced acute lung injury. J Biochem Mol Toxicol 2020; 34:e22515. [PMID: 32394537 DOI: 10.1002/jbt.22515] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 04/22/2020] [Indexed: 12/19/2022]
Abstract
In our previous study, we have confirmed that in phosgene-induced acute lung injury (ALI) rats, mesenchymal stem cells (MSCs) can treat the disease. Moreover, heat shock protein 70 (Hsp70) can be used as a protective protein, and Hsp70 upregulated drastically when exposed to stressful conditions. We aimed to assess that MSCs overexpressed Hsp70 could enhance the capacity of MSCs and have a good therapeutic effect on phosgene-induced ALI. We transduced MSCs with Hsp70 and then we tested the function of the transduced MSCs. Sprague Dawley rats inhaled phosgene in a closed container for 5 minutes. The transduced MSCs and MSCs were administered via the trachea immediately. Rats in each group were killed at 6, 24, and 48 hours after exposure. Compared to MSCs, MSCs overexpressed Hsp70 enhanced MSCs viability, antiapoptotic ability, and migration ability, and these effects disappeared when using the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway inhibitor. Furthermore, the results of pathological alterations improved. The lung wet-to-dry ratio declined. The lung injury index total protein content and total cells in bronchoalveolar lavage fluid (BALF) also declined. The level of tumor necrosis factor α declined and the level of interleukin-10 improved in BALF and serum. MSCs overexpressed Hsp70 can enhance the capacity and efficacy of MSCs in the treatment of phosgene-induced ALI and may be mediated through the PI3k/AKT signaling pathway. This article introduces a new approach to stem cell therapy for improving the efficacy of phosgene-induced ALI.
Collapse
Affiliation(s)
- Chaoyuan Jin
- Center of Emergency and Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China.,Medical Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China.,Medical Research Center for Chemical Injury, Emergency and Critical Care of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China
| | - Fangqing Zhou
- Center of Emergency and Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China.,Medical Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China.,Medical Research Center for Chemical Injury, Emergency and Critical Care of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China
| | - Lin Zhang
- Center of Emergency and Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China.,Medical Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China.,Medical Research Center for Chemical Injury, Emergency and Critical Care of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China
| | - Jie Shen
- Center of Emergency and Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China.,Medical Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China.,Medical Research Center for Chemical Injury, Emergency and Critical Care of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China
| |
Collapse
|
|
39
|
Identifying the Therapeutic Significance of Mesenchymal Stem Cells. Cells 2020; 9:cells9051145. [PMID: 32384763 PMCID: PMC7291143 DOI: 10.3390/cells9051145] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 05/04/2020] [Accepted: 05/05/2020] [Indexed: 12/12/2022] Open
Abstract
The pleiotropic behavior of mesenchymal stem cells (MSCs) has gained global attention due to their immense potential for immunosuppression and their therapeutic role in immune disorders. MSCs migrate towards inflamed microenvironments, produce anti-inflammatory cytokines and conceal themselves from the innate immune system. These signatures are the reason for the uprising in the sciences of cellular therapy in the last decades. Irrespective of their therapeutic role in immune disorders, some factors limit beneficial effects such as inconsistency of cell characteristics, erratic protocols, deviating dosages, and diverse transfusion patterns. Conclusive protocols for cell culture, differentiation, expansion, and cryopreservation of MSCs are of the utmost importance for a better understanding of MSCs in therapeutic applications. In this review, we address the immunomodulatory properties and immunosuppressive actions of MSCs. Also, we sum up the results of the enhancement, utilization, and therapeutic responses of MSCs in treating inflammatory diseases, metabolic disorders and diabetes.
Collapse
|
|
40
|
Liang H, Li W, Yang H, Cao Y, Ge L, Shi R, Fan Z, Dong R, Zhang C. FAM96B inhibits the senescence of dental pulp stem cells. Cell Biol Int 2020; 44:1193-1203. [DOI: 10.1002/cbin.11319] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 02/02/2020] [Indexed: 01/12/2023]
Affiliation(s)
- Hanbing Liang
- Department of EndodonticsCapital Medical University School of Stomatology Beijing 100050 China
| | - Wenzhi Li
- Department of EndodonticsCapital Medical University School of Stomatology Beijing 100050 China
| | - Haoqing Yang
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function ReconstructionCapital Medical University School of Stomatology Beijing 100050 China
| | - Yangyang Cao
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function ReconstructionCapital Medical University School of Stomatology Beijing 100050 China
| | - Lihua Ge
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function ReconstructionCapital Medical University School of Stomatology Beijing 100050 China
| | - Ruitang Shi
- Department of EndodonticsCapital Medical University School of Stomatology Beijing 100050 China
| | - Zhipeng Fan
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function ReconstructionCapital Medical University School of Stomatology Beijing 100050 China
| | - Rui Dong
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function ReconstructionCapital Medical University School of Stomatology Beijing 100050 China
| | - Chen Zhang
- Department of EndodonticsCapital Medical University School of Stomatology Beijing 100050 China
| |
Collapse
|
|
41
|
Hosseiniyan Khatibi SM, Kheyrolahzadeh K, Barzegari A, Rahbar Saadat Y, Zununi Vahed S. Medicinal signaling cells: A potential antimicrobial drug store. J Cell Physiol 2020; 235:7731-7746. [PMID: 32352173 DOI: 10.1002/jcp.29728] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 04/06/2020] [Accepted: 04/12/2020] [Indexed: 12/11/2022]
Abstract
Medicinal signaling cells (MSCs) are multipotent cells derived from mammalian bone marrow and periosteum that can be extended in culture. They can keep their ability in vitro to form a variety of mesodermal phenotypes and tissues. Over recent years, there has been great attention over MSCs since they can impact the organ transplantation as well as autoimmune and bacterial diseases. MSCs can secrete different bioactive factors such as growth factors, antimicrobial peptides/proteins and cytokines that can suppress the immune system and prevent infection via direct and indirect mechanisms. Moreover, MSCs are able to increase bacterial clearance in sepsis models by producing antimicrobial peptides such as defensins, cathelicidins, lipocalin and hepcidin. It is the aim of the present review to focus on the antibacterial effector functions of MSCs and their mechanisms of action against the pathogenic microbes.
Collapse
Affiliation(s)
| | - Keyvan Kheyrolahzadeh
- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.,Azad University, Tabriz Branch, Tabriz, Iran
| | - Abolfazl Barzegari
- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yalda Rahbar Saadat
- Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | | |
Collapse
|
|
42
|
Ali D, Chen L, Kowal JM, Okla M, Manikandan M, AlShehri M, AlMana Y, AlObaidan R, AlOtaibi N, Hamam R, Alajez NM, Aldahmash A, Kassem M, Alfayez M. Resveratrol inhibits adipocyte differentiation and cellular senescence of human bone marrow stromal stem cells. Bone 2020; 133:115252. [PMID: 31978617 DOI: 10.1016/j.bone.2020.115252] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Revised: 01/13/2020] [Accepted: 01/20/2020] [Indexed: 12/16/2022]
Abstract
Bone marrow adipose tissue (BMAT) is a unique adipose depot originating from bone marrow stromal stem cells (BMSCs) and regulates bone homeostasis and energy metabolism. An increased BMAT volume is observed in several conditions e.g. obesity, type 2 diabetes, osteoporosis and is known to be associated with bone fragility and increased risk for fracture. Therapeutic approaches to decrease the accumulation of BMAT are clinically relevant. In a screening experiment of natural compounds, we identified Resveratrol (RSV), a plant-derived antioxidant mediating biological effects via sirtuin- related mechanisms, to exert significant effects of BMAT formation. Thus, we examined in details the effects RSV on adipocytic and osteoblastic differentiation of tolermerized human BMSCs (hBMSC-TERT). RSV (1.0 μM) enhanced osteoblastic differentiation and inhibited adipocytic differentiation of hBMSC-TERT when compared with control and Sirtinol (Sirtuin inhibitor). Global gene expression profiling and western blot analysis revealed activation of a number of signaling pathways including focal adhesion kinase (FAK). Pharmacological inhibition of FAK using (PF-573228) and AKT inhibitor (LY-294002) (5μM), diminished RSV-induced osteoblast differentiation. In addition, RSV reduced the levels of senescence-associated secretory phenotype (SASP), gene markers associated with senescence (P53, P16, and P21), intracellular ROS levels and increased gene expression of enzymes protecting cells from oxidative damage (HMOX1 and SOD3). In vitro treatment of primary hBMSCs from aged patients characterized with high adipocytic and low osteoblastic differentiation ability with RSV, significantly enhanced osteoblast and decreased adipocyte formation when compared to hBMSCs from young donors. RSV targets hBMSCs and inhibits adipogenic differentiation and senescence-associated phenotype and thus a potential agent for treating conditions of increased BMAT formation.
Collapse
Affiliation(s)
- Dalia Ali
- Molecular Endocrinology & Stem Cell Research Unit (KMEB), Department of Endocrinology & Metabolism, University Hospital of Odense and University of Southern Denmark, Odense, Denmark.
| | - Li Chen
- Molecular Endocrinology & Stem Cell Research Unit (KMEB), Department of Endocrinology & Metabolism, University Hospital of Odense and University of Southern Denmark, Odense, Denmark.
| | - Justyna M Kowal
- Molecular Endocrinology & Stem Cell Research Unit (KMEB), Department of Endocrinology & Metabolism, University Hospital of Odense and University of Southern Denmark, Odense, Denmark.
| | - Meshail Okla
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
| | - Muthurangan Manikandan
- Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
| | - Moayad AlShehri
- Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
| | - Yousef AlMana
- Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
| | - Reham AlObaidan
- Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
| | - Najd AlOtaibi
- Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
| | - Rimi Hamam
- Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
| | - Nehad M Alajez
- Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
| | - Abdullah Aldahmash
- Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Prince Naif Health Research Center, King Saud University, Riyadh, Saudi Arabia.
| | - Moustapha Kassem
- Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Molecular Endocrinology & Stem Cell Research Unit (KMEB), Department of Endocrinology & Metabolism, University Hospital of Odense and University of Southern Denmark, Odense, Denmark; Department of Cellular and Molecular Medicine, Danish Stem Cell Center (DanStem), University of Copenhagen, 2200 Copenhagen, Denmark.
| | - Musaad Alfayez
- Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
| |
Collapse
|
|
43
|
Lv H, Liu Q, Sun Y, Yi X, Wei X, Liu W, Zhang Q, Yi H, Chen G. Mesenchymal stromal cells ameliorate acute lung injury induced by LPS mainly through stanniocalcin-2 mediating macrophage polarization. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:334. [PMID: 32355778 PMCID: PMC7186596 DOI: 10.21037/atm.2020.02.105] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background Acute lung injury (ALI) is a devastating syndrome with no effective pharmacological therapies in the clinic. Mesenchymal stromal cells (MSCs) have been demonstrated to promote inflammation resolution and tissue repair in ALI. However, the specific mechanisms of this have not been clearly elucidated. Stanniocalcin-2 (STC2) is a stress-responsive protein that has anti-oxidative properties. Our previous study found that STC2 is a highly expressed stanniocalcin in MSCs, which may be involved in immunomodulatory activities. However, the role of STC2 in MSCs to resolve ALI has never been elucidated. Methods Specific shRNA was used to downregulate STC2 in MSCs. We detected ROS, cell apoptosis, and paracrine factors changes in MSCs. STC2-associated antioxidant genes were also investigated by Co-immunoprecipitation (Co-IP) and immunofluorescence. Macrophage (THP1 cells) phenotype transitions were measured by flow cytometry after coculturing with MSCs in vitro. Then, we used MSCs to treat LPS-induced ALI in mice, and assessed injury scores inflammation, and antioxidant activities in the lungs of the mice. Alveolar macrophage (AM) phenotypes and CFSE-labeled MSC apoptosis in collected bronchoalveolar fluids (BALF) were also analyzed by flow cytometry. Results After the STC2 knockdown, MSCs increased ROS generation and cell apoptosis after PX12 pretreatment. The antioxidant protein Nrf2 was colocalized with STC2 in the nucleus. A lack of STC2 expression in MSCs produced less interleukin 10 (IL10) and blunted macrophage polarization in THP1 cells. Furthermore, in the murine LPS-induced ALI model, the STC2 knockdown counteracted the inflammatory resolution and antioxidative effect of MSCs in the lungs. MSCshSTC2-treated mice had a higher lung injury score than the controls, which may be attributed to diminished AM polarization and increased apoptosis of MSCs in vivo. Conclusions Collectively, these results suggested that STC2 is essential to the anti-oxidative and anti-inflammation properties of MSCs and could prove to be crucial for stem cell therapies for ALI.
Collapse
Affiliation(s)
- Haijin Lv
- Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.,Key Laboratory of Liver Disease Biotherapy and Translational Medicine of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou 510630, China
| | - Qiuli Liu
- Key Laboratory of Liver Disease Biotherapy and Translational Medicine of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou 510630, China.,The Biotherapy Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Yao Sun
- Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Xiaomeng Yi
- Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Xuxia Wei
- Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Wei Liu
- Key Laboratory of Liver Disease Biotherapy and Translational Medicine of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou 510630, China.,Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Qi Zhang
- Key Laboratory of Liver Disease Biotherapy and Translational Medicine of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou 510630, China.,The Biotherapy Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Huimin Yi
- Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Guihua Chen
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.,Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou 510630, China
| |
Collapse
|
|
44
|
Nahand JS, Mahjoubin-Tehran M, Moghoofei M, Pourhanifeh MH, Mirzaei HR, Asemi Z, Khatami A, Bokharaei-Salim F, Mirzaei H, Hamblin MR. Exosomal miRNAs: novel players in viral infection. Epigenomics 2020; 12:353-370. [PMID: 32093516 PMCID: PMC7713899 DOI: 10.2217/epi-2019-0192] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 01/06/2020] [Indexed: 12/21/2022] Open
Abstract
Exosomes are secreted nanovesicles that are able to transfer their cargo (such as miRNAs) between cells. To determine to what extent exosomes and exosomal miRNAs are involved in the pathogenesis, progression and diagnosis of viral infections. The scientific literature (PubMed and Google Scholar) was searched from 1970 to 2019. The complex biogenesis of exosomes and miRNAs was reviewed. Exosomes contain both viral and host miRNAs that can be used as diagnostic biomarkers for viral diseases. Viral proteins can alter miRNAs, and conversely miRNAs can alter the host response to viral infections in a positive or negative manner. It is expected that exosomal miRNAs will be increasingly used for diagnosis, monitoring and even treatment of viral infections.
Collapse
Affiliation(s)
- Javid Sadri Nahand
- Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Student Research Committee, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Mahjoubin-Tehran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Moghoofei
- Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | | | - Hamid Reza Mirzaei
- Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry & Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Alireza Khatami
- Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Farah Bokharaei-Salim
- Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry & Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Michael R Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA 02114, USA
| |
Collapse
|
|
45
|
HMOX1 is partly responsible for phenotypic and functional abnormalities in mesenchymal stem cells/stromal cells from placenta of preeclampsia (PE) patients. Stem Cell Res Ther 2020; 11:30. [PMID: 31964423 PMCID: PMC6975087 DOI: 10.1186/s13287-020-1557-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 12/19/2019] [Accepted: 01/08/2020] [Indexed: 01/12/2023] Open
Abstract
Background Preeclampsia is a common obstetric syndrome affecting women in their first pregnancy and characterized by hypertension and proteinuria, which appears after 20 weeks of gestation. It is characterized by high blood pressure and occasional damage to another organ system most often the liver and kidneys. Currently, the etiology and pathogenesis of this syndrome are not fully understood. Since mesenchymal stem cells/stromal cells (MSCs) are intimately associated with endothelial cells that line vessel walls in the decidua they may play some role in the pathogenesis of this syndrome. In this study, we have partly, unveiled the mechanism of preeclampsia pathogenesis at the stem cells level. Methods We have isolated and characterized MSCs from decidua basalis of preeclampsia placenta (PE-DBMSCs) and showed their decreased functionality in terms of proliferation, migration, adhesion and clone formation potential as compared to MSCs isolated from decidua region of normal placentae (DBMSCs). The cells were preconditioned with H2O2 and the functional characteristics were evaluated. Differentially expressed genes were analyzed using mass spectrometry. Immunoblotting confirmed the expression of these proteins. Results Pre-conditioning with H2O2 restored the functional outcome of PE-DBMSCs. Mass spectrometry (MS) analysis of differentially expressed proteins revealed HMOX1 as one of the major candidates missing in PE-DBMSCs. HMOX1 inhibition by tin protoporphyrin (SnPP) in normal DBMSCs resulted in a reduction in proliferation, migration, adhesion, and clone formation processes as compared to the untreated controls. mRNA and protein analyses of PE-DBMSCs preconditioned with H2O2 at lower doses showed upregulation of HMOX1 expression. Conclusions We hereby show for the first time that loss of function of stem cells/stromal cells isolated from the patients with preeclampsia may contribute towards the disease exacerbation. Our results suggest that HMOX1 may be partially responsible for the loss of functionality in PE-DBMSCs and contribute significantly towards the pathophysiology of preeclampsia. However, further investigation is required to decipher its exact role in the development and onset of the disorder.
Collapse
|
|
46
|
Kim K, Bou-Ghannam S, Okano T. Cell sheet tissue engineering for scaffold-free three-dimensional (3D) tissue reconstruction. Methods Cell Biol 2020; 157:143-167. [PMID: 32334713 DOI: 10.1016/bs.mcb.2019.11.020] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Three-dimensional (3D) reconstruction of highly functional tissues is of great importance in advancing the clinical benefit of tissue engineering and regenerative medicine. In the last quarter century, many studies have found that by engineering a 3D microenvironment that resembles the in vivo tissue condition, cells exhibit behaviors and functions that reflect those of native tissue. Biomaterial scaffolds are a central technology for providing 3D microenvironments in vitro, and, in conjunction with diverse design and cell seeding advents, have produced highly functional and complex 3D tissues. Here, we describe a new approach to creating 3D cell-dense tissue-like constructs without a biomaterial scaffold. Cell sheet technology with cell sheet layering strategies generates highly cell dense, engineered tissue capable of direct crosstalk with the tissue-engraftment surface, in addition to paracrine-mediated signaling. In this chapter, we will introduce methods of reconstructing 3D tissue using cell sheet technology and the advantages of a scaffold-free design.
Collapse
Affiliation(s)
- Kyungsook Kim
- Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, Salt Lake City, UT, United States.
| | - Sophia Bou-Ghannam
- Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, Salt Lake City, UT, United States; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, United States
| | - Teruo Okano
- Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, Salt Lake City, UT, United States; Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
| |
Collapse
|
|
47
|
Ghorbani A, Sadeghnia HR, Afshari AR, Hosseini A. Rosmarinic Acid Protects Adipose Tissue-Derived Mesenchymal Stem Cells in Nutrient-Deficient Conditions. Prev Nutr Food Sci 2020; 24:449-455. [PMID: 31915641 PMCID: PMC6941722 DOI: 10.3746/pnf.2019.24.4.449] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 11/04/2019] [Indexed: 11/06/2022] Open
Abstract
One of the major challenges for stem cell therapy of ischemic organs is that the transplanted cells are confronted with nutrient deficiency and oxidative stress. Previous studies have indicated that pretreatment of stem cells with cytoprotective phytochemicals improves their therapeutic potential. This study was aimed to investigate whether rosmarinic acid can enhance survival of adipose tissue-derived stem cells (ASCs) in nutrient-deficient culture as an in vitro model of ischemia. The ASCs were isolated from subcutaneous adipose tissue of male adult Wistar rats and incubated for 24 h with rosmarinic acid in nutrient-deficient (glucose- and serum-deprived, GSD) culture medium. In a separate experiment, ASCs were pre-incubated for 4 h with rosmarinic acid and then exposed to GSD conditions for 24 h. The viability of ASCs was determined using thiazolyl blue tetrazolium bromide assays. The effect of rosmarinic acid on the cell cycle was evaluated using propidium iodide staining. GSD conditions significantly decreased the viability of ASCs and enhanced the generation of reactive oxygen species (ROS), lipid peroxidation, sub-G1 cell populations, and necrosis. Both pre-incubation and incubation of ASCs with 0.75~6 μM rosmarinic acid significantly increased cell viability in GSD conditions. Rosmarinic acid further decreased the level of ROS, lipid peroxidation, the percent of cells in sub-G1 stage, and necrosis in GSD conditions. These findings suggest that rosmarinic acid enhances survival of ASCs cultured in nutrient-deficient conditions through promoting antioxidant effects. Therefore, rosmarinic acid may help preserve ASCs survival after they are transplanted into ischemic organs.
Collapse
Affiliation(s)
- Ahmad Ghorbani
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad 91779-44553, Iran
| | - Hamid Reza Sadeghnia
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad 91779-44553, Iran
| | - Amir Reza Afshari
- Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd 94149-74877, Iran
| | - Azar Hosseini
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad 91779-44553, Iran
| |
Collapse
|
|
48
|
Choi YJ, Lee CM, Lee JH, Park SH, Nam MJ. Protective effects of hepatocyte growth factor gene overexpression against hydrogen peroxide-induced apoptosis in mesenchymal stem cells. ENVIRONMENTAL TOXICOLOGY 2019; 34:1236-1245. [PMID: 31313457 DOI: 10.1002/tox.22824] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 06/19/2019] [Accepted: 06/26/2019] [Indexed: 06/10/2023]
Abstract
Hepatocyte growth factor (HGF) has recently been reported to exhibit antioxidant and antiapoptotic effects. Therefore, we investigated the effect of overexpression of HGF gene in H2 O2 -treated mesenchymal stem cells (MSCs). HGF-overexpression increased the cell viability from 50% to 84%, decreased the population of apoptotic cells from 20% to 16%, and decreased the intracellular reactive oxygen species (ROS) levels from 127% to 100% in cells treated with H2 O2 . HGF suppression decreased the cell viability from 58% to 36%, increased the population of apoptotic cells from 23 to 81%, and increased the intracellular ROS levels from 181% to 240% in cells exposed to H2 O2 . HGF-overexpression also reduced the expression levels of proapoptotic proteins in MSCs treated with H2 O2 . Phosphorylation of extracellular signal-regulated kinases, c-Jun amino-terminal kinases, and p38, which was induced by H2 O2 , decreased in MSCs overexpressing the HGF gene. Taken together, our results suggest that HGF has a protective effect on H2 O2 -induced apoptosis in MSCs.
Collapse
Affiliation(s)
- Yong Jun Choi
- Department of Biological Sciences, Gachon University, Seongnam-si, Republic of Korea
| | - Chang Min Lee
- Department of Biological Sciences, Gachon University, Seongnam-si, Republic of Korea
| | - Jeong Hyun Lee
- Department of Biological Sciences, Gachon University, Seongnam-si, Republic of Korea
| | - See-Hyoung Park
- Department of Bio and Chemical Engineeing, Hongik University, Sejong, Republic of Korea
| | - Myeong Jin Nam
- Department of Biological Sciences, Gachon University, Seongnam-si, Republic of Korea
| |
Collapse
|
|
49
|
Xu AL, Rodriguez LA, Walker KP, Mohammadipoor A, Kamucheka RM, Cancio LC, Batchinsky AI, Antebi B. Mesenchymal Stem Cells Reconditioned in Their Own Serum Exhibit Augmented Therapeutic Properties in the Setting of Acute Respiratory Distress Syndrome. Stem Cells Transl Med 2019; 8:1092-1106. [PMID: 31219247 PMCID: PMC6766690 DOI: 10.1002/sctm.18-0236] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 04/03/2019] [Indexed: 12/13/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are a promising form of therapy for acute respiratory distress syndrome (ARDS). The objective of this study was twofold: (a) to characterize cytokine expression in serum from ARDS subjects receiving MSCs and (b) to determine MSC function following “preconditioning” with ARDS serum. In phase I, serum from three cohorts of animals (uninjured [no ARDS, n = 4], injured untreated [n = 5], and injured treated with approximately 6 million per kilogram MSCs [n = 7]) was analyzed for expression of inflammatory mediators. In phase II, the functional properties of bone marrow porcine MSCs were assessed following “preconditioning” with serum from the three cohorts. In phase III, the findings from the previous phases were validated using human bone marrow MSCs (hBM‐MSCs) and lipopolysaccharide (LPS). Serum from injured treated animals had significantly lower levels of interferon‐γ and significantly higher levels of interleukin (IL)‐1 receptor antagonist (IL‐1RA) and IL‐6. Similarly, upon exposure to the injured treated serum ex vivo, the MSCs secreted higher levels of IL‐1RA and IL‐10, dampened the secretion of proinflammatory cytokines, exhibited upregulation of toll‐like receptor 4 (TLR‐4) and vascular endothelial growth factor (VEGF) genes, and triggered a strong immunomodulatory response via prostaglandin E2 (PGE2). hBM‐MSCs demonstrated a similar augmented therapeutic function following reconditioning in a LPS milieu. Administration of MSCs modulated the inflammatory milieu following ARDS. Exposure to ARDS serum ex vivo paralleled the trends seen in vivo, which appear to be mediated, in part, through TLR‐4 and VEGF and PGE2. Reconditioning MSCs in their own serum potentiates their immunotherapeutic function, a technique that can be used in clinical applications. stem cells translational medicine2019;8:1092–1106
Collapse
Affiliation(s)
- Amy L Xu
- Department of Expeditionary Critical Care, U.S. Army Institute of Surgical Research, San Antonio, Texas, USA.,Department of Human Biology, Stanford University, Stanford, California, USA
| | - Luis A Rodriguez
- Department of Expeditionary Critical Care, U.S. Army Institute of Surgical Research, San Antonio, Texas, USA.,Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA
| | - Kerfoot P Walker
- Department of Expeditionary Critical Care, U.S. Army Institute of Surgical Research, San Antonio, Texas, USA.,Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA
| | - Arezoo Mohammadipoor
- Department of Expeditionary Critical Care, U.S. Army Institute of Surgical Research, San Antonio, Texas, USA.,Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA
| | - Robin M Kamucheka
- Department of Expeditionary Critical Care, U.S. Army Institute of Surgical Research, San Antonio, Texas, USA
| | - Leopoldo C Cancio
- Department of Expeditionary Critical Care, U.S. Army Institute of Surgical Research, San Antonio, Texas, USA
| | - Andriy I Batchinsky
- Department of Expeditionary Critical Care, U.S. Army Institute of Surgical Research, San Antonio, Texas, USA.,The Geneva Foundation, Tacoma, Washington, USA
| | - Ben Antebi
- Department of Expeditionary Critical Care, U.S. Army Institute of Surgical Research, San Antonio, Texas, USA.,Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, Texas, USA
| |
Collapse
|
|
50
|
Zhou W, Lin J, Zhao K, Jin K, He Q, Hu Y, Feng G, Cai Y, Xia C, Liu H, Shen W, Hu X, Ouyang H. Single-Cell Profiles and Clinically Useful Properties of Human Mesenchymal Stem Cells of Adipose and Bone Marrow Origin. Am J Sports Med 2019; 47:1722-1733. [PMID: 31100005 DOI: 10.1177/0363546519848678] [Citation(s) in RCA: 137] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) can be isolated from various tissues and can present themselves as a promising cell source for cell-based therapies. Although adipose- and bone marrow-derived mesenchymal stem cells have already been used in a considerable number of clinical trials for osteoarthritis treatment, systematic analyses from single- to bulk-cell resolution as well as clinical outcomes of these 2 MSCs are still insufficient. PURPOSE To explore the characteristics and differences of adipose-derived stem cells (ADSCs) and bone marrow MSCs (BMSCs) at single- and bulk-cell levels, to study the clinical outcomes of these 2 cells on the treatment of osteoarthritis, and to provide potential guidance on the more precise clinical application of these MSCs. STUDY DESIGN Controlled laboratory study and meta-analysis. METHODS Same donor-derived ADSCs and BMSCs were isolated and cultured. Single- and bulk-cell assays were used to identify the characteristics of these 2 cells. Meta-analysis of clinical trials was done to compare the clinical therapeutic effects in osteoarthritis treatment with ADSCs and BMSCs. RESULTS Single-cell RNA sequencing analysis showed that the population of ADSCs showed lower transcriptomic heterogeneity when compared with BMSCs. Additionally, as compared with BMSCs, ADSCs were less dependent on mitochondrial respiration for energy production. Furthermore, ADSCs had a lower expression level of human leukocyte antigen class I antigen and higher immunosuppression capacity when compared with the BMSC population. Meta-analysis of current clinical trials of osteoarthritis treatment with MSCs consistently showed that ADSCs are more stable than BMSCs in their therapeutic effect. CONCLUSION These results provide basic biological insights into human ADSCs and BMSCs at the single-cell resolution. Findings indicated that ADSCs may be a more controllable stem cell source, may be more adaptable to surviving in the hypoxic articular cavity niche, and may exhibit superiority in regulating inflammation. Based on the meta-analysis results of the different characteristics of ADSCs and BMSCs, ADSCs were implicated as being a better cell source for osteoarthritis treatment. CLINICAL RELEVANCE These results guide a more precise clinical application of adipose and bone marrow mesenchymal stem cells.
Collapse
Affiliation(s)
- Wenyan Zhou
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| | - Junxin Lin
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| | - Kun Zhao
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| | - Kaixiu Jin
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| | - Qiulin He
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| | - Yejun Hu
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| | - Gang Feng
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| | - Youzhi Cai
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| | - Chen Xia
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| | - Hua Liu
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| | - Weiliang Shen
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| | - Xueqing Hu
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| | - Hongwei Ouyang
- Investigation performed at the School of Medicine, Zhejiang University, Hangzhou, China
| |
Collapse
|