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Le NT, Dunleavy MW, Kumar RD, Zhou W, Bhatia SS, El-Hashash AH. Cellular therapies for idiopathic pulmonary fibrosis: current progress and future prospects. AMERICAN JOURNAL OF STEM CELLS 2024; 13:191-211. [PMID: 39308764 PMCID: PMC11411253 DOI: 10.62347/daks5508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 07/17/2024] [Indexed: 09/25/2024]
Abstract
Idiopathic pulmonary fibrosis (IPF) is an interstitial, fibrotic lung disease characterized by progressive damage. Lung tissues with IPF are replaced by fibrotic tissues with increased collagen deposition, modified extracellular matrix, all which overall damages the alveoli. These changes eventually impede the gas exchange function of the alveoli, and eventually leads to fatal respiratory failure of the lung. Investigations have been conducted to further understand IPF's pathogenesis, and significant progress in understanding its development has been made. Additionally, two therapeutic treatments, Nintedanib and Pirfenidone, have been approved and are currently used in medical applications. Moreover, cell-based treatments have recently come to the forefront of developing disease therapeutics and are the focus of many current studies. Furthermore, a sizable body of research encompassing basic, pre-clinical, and even clinical trials have all been amassed in recent years and hold a great potential for more widespread applications in patient care. Herein, this article reviews the progress in understanding the pathogenesis and pathophysiology of IPF. Additionally, different cell types used in IPF therapy were reviewed, including alveolar epithelial cells (AECs), circulating endothelial progenitors (EPCs), mixed lung epithelial cells, different types of stem cells, and endogenous lung tissue-specific stem cells. Finally, we discussed the contemporary trials that employ or explore cell-based therapy for IPF.
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Affiliation(s)
- Nicholas T Le
- Biology Department, Texas A&M University College Station, TX, USA
| | | | - Rebecca D Kumar
- Biology Department, Texas A&M University College Station, TX, USA
| | - William Zhou
- The University of Texas at Austin Austin, TX, USA
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Wei P, Jia M, Kong X, Lyu W, Feng H, Sun X, Li J, Yang JJ. Human umbilical cord-derived mesenchymal stem cells ameliorate perioperative neurocognitive disorder by inhibiting inflammatory responses and activating BDNF/TrkB/CREB signaling pathway in aged mice. Stem Cell Res Ther 2023; 14:263. [PMID: 37735415 PMCID: PMC10512658 DOI: 10.1186/s13287-023-03499-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 09/14/2023] [Indexed: 09/23/2023] Open
Abstract
BACKGROUND Perioperative neurocognitive disorder (PND) is a key complication affecting older individuals after anesthesia and surgery. Failure to translate multiple pharmacological therapies for PND from preclinical studies to clinical settings has necessitated the exploration of novel therapeutic strategies. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) treatment has emerged as a promising therapeutic strategy for treating neurodegenerative diseases and has the potential to translate basic science into clinical practice. In this study, we investigated the effects and underlying mechanism of hUC-MSCs on PND in aged mice. METHODS hUC-MSCs were isolated from an infant umbilical cord and identified using flow cytometry and differentiation assays. We established PND model by undergoing aseptic laparotomy under isoflurane anesthesia maintaining spontaneous ventilation in eighteen-month-old male C57BL/6 mice. hUC-MSCs were slowly injected into mice by coccygeal vein before anesthesia. Cognitive function, systemic and neuroinflammatory responses, neuroplasticity, endogenous neurogenesis, and brain-derived neurotrophic factor (BDNF) were assessed. To determine the brain mechanisms underlying by which hUC-MSCs mediate their neuroprotective effects in PND, K252a, an antagonist of BDNF receptor, was administered intraperitoneally before surgery. Hippocampal BDNF/TrkB/CREB signaling pathway and metabolomic signatures were evaluated. RESULTS hUC-MSC treatment ameliorated the learning and memory impairment in aged mice with PND. The downstream effects were the suppression of systemic and hippocampal inflammation and restoration of neurogenesis and neuroplasticity dysregulation. Interestingly, the level of mature BDNF, but not that of proBDNF, was increased in the hippocampus after hUC-MSC treatment. Further analysis revealed that the improved cognitive recovery and the restoration of neurogenesis and neuroplasticity dysregulation elicited by exposure to hUC-MSCs were, at least partially, mediated by the activation of the BDNF/TrkB/CREB signaling pathway. Untargeted metabolomic further identified lipid metabolism dysfunction as potential downstream of the BDNF/TrkB/CREB signaling pathway in hUC-MSC-mediated neuroprotection for PND. CONCLUSIONS Our study highlights the beneficial effects of hUC-MSC treatment on PND and provides a justification to consider the potential use of hUC-MSCs in the perioperative period.
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Affiliation(s)
- Penghui Wei
- Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, People's Republic of China
- Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, People's Republic of China
- Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, People's Republic of China
- Henan Province International Joint Laboratory of Pain, Cognition and Emotion, Zhengzhou, People's Republic of China
| | - Min Jia
- Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, People's Republic of China
- Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, People's Republic of China
- Henan Province International Joint Laboratory of Pain, Cognition and Emotion, Zhengzhou, People's Republic of China
| | - Xiangyi Kong
- Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, People's Republic of China
| | - Wenyuan Lyu
- Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, People's Republic of China
| | - Hao Feng
- Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, People's Republic of China
| | - Xinyi Sun
- Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, People's Republic of China
| | - Jianjun Li
- Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, People's Republic of China
- Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Jian-Jun Yang
- Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, People's Republic of China.
- Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, People's Republic of China.
- Henan Province International Joint Laboratory of Pain, Cognition and Emotion, Zhengzhou, People's Republic of China.
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Cheung KCP, Jiao M, Xingxuan C, Wei J. Extracellular vesicles derived from host and gut microbiota as promising nanocarriers for targeted therapy in osteoporosis and osteoarthritis. Front Pharmacol 2023; 13:1051134. [PMID: 36686680 PMCID: PMC9859449 DOI: 10.3389/fphar.2022.1051134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 12/21/2022] [Indexed: 01/08/2023] Open
Abstract
Osteoporosis (OP), a systemic bone disease that causes structural bone loss and bone mass loss, is often associated with fragility fractures. Extracellular vesicles (EVs) generated by mammalian and gut bacteria have recently been identified as important mediators in the intercellular signaling pathway that may play a crucial role in microbiota-host communication. EVs are tiny membrane-bound vesicles, which range in size from 20 to 400 nm. They carry a variety of biologically active substances across intra- and intercellular space. These EVs have developed as a promising research area for the treatment of OP because of their nanosized architecture, enhanced biocompatibility, reduced toxicity, drug loading capacity, ease of customization, and industrialization. This review describes the latest development of EVs derived from mammals and bacteria, including their internalization, isolation, biogenesis, classifications, topologies, and compositions. Additionally, breakthroughs in chemical sciences and the distinctive biological features of bacterial extracellular vesicles (BEVs) allow for the customization of modified BEVs for the therapy of OP. In conclusion, we give a thorough and in-depth summary of the main difficulties and potential future of EVs in the treatment of OP, as well as highlight innovative uses and choices for the treatment of osteoarthritis (OA).
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Affiliation(s)
- Kenneth Chat Pan Cheung
- Hong Kong Traditional Chinese Medicine Phenome Research Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Ma Jiao
- Hong Kong Traditional Chinese Medicine Phenome Research Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Chen Xingxuan
- Hong Kong Traditional Chinese Medicine Phenome Research Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Jia Wei
- Hong Kong Traditional Chinese Medicine Phenome Research Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
- Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
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Rybachuk O, Savytska N, Pinet É, Yaminsky Y, Medvediev V. Heterogeneous pHPMA hydrogel promotes neuronal differentiation of bone marrow derived stromal cells in vitroand in vivo. Biomed Mater 2023; 18. [PMID: 36542861 DOI: 10.1088/1748-605x/acadc3] [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: 06/27/2022] [Accepted: 12/21/2022] [Indexed: 12/24/2022]
Abstract
Synthetic hydrogels composed of polymer pore frames are commonly used in medicine, from pharmacologically targeted drug delivery to the creation of bioengineering constructions used in implantation surgery. Among various possible materials, the most common are poly-[N(2-hydroxypropyl)methacrylamide] (pHPMA) derivatives. One of the pHPMA derivatives is biocompatible hydrogel, NeuroGel. Upon contact with nervous tissue, the NeuroGel's structure can support the chemical and physiological conditions of the tissue necessary for the growth of native cells. Owing to the different pore diameters in the hydrogel, not only macromolecules, but also cells can migrate. This study evaluated the differentiation of bone marrow stromal cells (BMSCs) into neurons, as well as the effectiveness of using this biofabricated system in spinal cord injuryin vivo. The hydrogel was populated with BMSCs by injection or rehydration. After cultivation, these fragments (hydrogel + BMSCs) were implanted into the injured rat spinal cord. Fragments were immunostained before implantation and seven months after implantation. During cultivation with the hydrogel, both variants (injection/rehydration) of the BMSCs culture retained their viability and demonstrated a significant number of Ki-67-positive cells, indicating the preservation of their proliferative activity. In hydrogel fragments, BMSCs also maintained their viability during the period of cocultivation and were Ki-67-positive, but in significantly fewer numbers than in the cell culture. In addition, in fragments of hydrogel with grafted BMSCs, both by the injection or rehydration versions, we observed a significant number up to 57%-63.5% of NeuN-positive cells. These results suggest that the heterogeneous pHPMA hydrogel promotes neuronal differentiation of bone marrow-derived stromal cells. Furthermore, these data demonstrate the possible use of NeuroGel implants with grafted BMSCs for implantation into damaged areas of the spinal cord, with subsequent nerve fiber germination, nerve cell regeneration, and damaged segment restoration.
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Affiliation(s)
- Oksana Rybachuk
- Bogomoletz Institute of Physiology NAS of Ukraine, Kyiv, Ukraine.,Institute of Genetic and Regenerative Medicine, M. D. Strazhesko National Scientific Center of Cardiology, Clinical and Regenerative Medicine, NAMS of Ukraine, Kyiv, Ukraine
| | - Natalia Savytska
- Bogomoletz Institute of Physiology NAS of Ukraine, Kyiv, Ukraine.,German Center for Neurodegenerative Diseases, Tübingen, Germany
| | | | - Yurii Yaminsky
- State Institution 'Romodanov Neurosurgery Institute, NAMS of Ukraine', Kyiv, Ukraine
| | - Volodymyr Medvediev
- Bogomoletz Institute of Physiology NAS of Ukraine, Kyiv, Ukraine.,Bogomolets National Medical University, Kyiv, Ukraine
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Ray SK, Mukherjee S. Mesenchymal Stem Cells Derived from Umbilical Cord Blood having Excellent Stemness Properties with Therapeutic Benefits - a New Era in Cancer Treatment. Curr Stem Cell Res Ther 2022; 17:328-338. [PMID: 35469574 DOI: 10.2174/1574888x17666220425102154] [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: 12/25/2021] [Revised: 02/18/2022] [Accepted: 03/03/2022] [Indexed: 11/22/2022]
Abstract
Mesenchymal stem cells (MSCs) are the most promising candidates for cellular therapies, and most therapeutic applications have focused on MSCs produced from adult bone marrow, despite mounting evidence that MSCs are present in a wide range of conditions. Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells, but its therapeutic potential extends beyond the hematopoietic component, which also suggests solid organ regenerative potential. With potential ranging from embryonic-like to lineage-committed progenitor cells, many different stems and progenitor cell populations have been postulated. MSC is currently inferred by numerous clinical applications for human UCB. aAs stem cell therapy kicks off some new research and these cells show such a boon to stem cell therapy, it is nevertheless characteristic that the prospect of UCB conservation is gaining momentum. Taken together, the experience described here shows that MSCs derived from UCB are seen as attractive therapeutic candidates for various human disorders including cancer. It is argued that a therapeutic stem cell transplant, using stem cells from UCB, provides a reliable repository of early precursor cells that can be useful in a large number of different conditions, considering issues of safety, availability, transplant methodology, rejection, and side effects. In particular, we focus on the concept of isolation and expansion, comparing the phenotype with MSC derived from the UCB, describing the ability to differentiate, and lastly, the therapeutic potential concerning stromal support, stemness characteristic, immune modulation, and cancer stem cell therapy. Thus it is an overview of the therapeutic application of UCB derived MSCs, with a special emphasis on cancer. Besides, the current evidence on the double-edged sword of MSCs in cancer treatment and the latest advances in UCB-derived MSC in cancer research will be discussed.
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Affiliation(s)
| | - Sukhes Mukherjee
- Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh-462020, India
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Anudeep TC, Jeyaraman M, Muthu S, Rajendran RL, Gangadaran P, Mishra PC, Sharma S, Jha SK, Ahn BC. Advancing Regenerative Cellular Therapies in Non-Scarring Alopecia. Pharmaceutics 2022; 14:612. [PMID: 35335987 PMCID: PMC8953616 DOI: 10.3390/pharmaceutics14030612] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/28/2022] [Accepted: 03/07/2022] [Indexed: 02/05/2023] Open
Abstract
Alopecia or baldness is a common diagnosis in clinical practice. Alopecia can be scarring or non-scarring, diffuse or patchy. The most prevalent type of alopecia is non-scarring alopecia, with the majority of cases being androgenetic alopecia (AGA) or alopecia areata (AA). AGA is traditionally treated with minoxidil and finasteride, while AA is treated with immune modulators; however, both treatments have significant downsides. These drawbacks compel us to explore regenerative therapies that are relatively devoid of adverse effects. A thorough literature review was conducted to explore the existing proven and experimental regenerative treatment modalities in non-scarring alopecia. Multiple treatment options compelled us to classify them into growth factor-rich and stem cell-rich. The growth factor-rich group included platelet-rich plasma, stem cell-conditioned medium, exosomes and placental extract whereas adult stem cells (adipose-derived stem cell-nano fat and stromal vascular fraction; bone marrow stem cell and hair follicle stem cells) and perinatal stem cells (umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), Wharton jelly-derived MSCs (WJ-MSCs), amniotic fluid-derived MSCs (AF-MSCs), and placental MSCs) were grouped into the stem cell-rich group. Because of its regenerative and proliferative capabilities, MSC lies at the heart of regenerative cellular treatment for hair restoration. A literature review revealed that both adult and perinatal MSCs are successful as a mesotherapy for hair regrowth. However, there is a lack of standardization in terms of preparation, dose, and route of administration. To better understand the source and mode of action of regenerative cellular therapies in hair restoration, we have proposed the "À La Mode Classification". In addition, available evidence-based cellular treatments for hair regrowth have been thoroughly described.
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Affiliation(s)
- Talagavadi Channaiah Anudeep
- Department of Plastic Surgery, Topiwala National Medical College and BYL Nair Ch. Hospital, Mumbai 400008, India;
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India; (M.J.); (S.M.); (S.K.J.)
- À La Mode Esthétique Studio, Mysuru 570011, India
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
| | - Madhan Jeyaraman
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India; (M.J.); (S.M.); (S.K.J.)
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
- Department of Orthopaedics, Faculty of Medicine—Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, India
| | - Sathish Muthu
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India; (M.J.); (S.M.); (S.K.J.)
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624304, India
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Korea
| | - Prabhu Chandra Mishra
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
| | - Shilpa Sharma
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
- Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India; (M.J.); (S.M.); (S.K.J.)
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Korea
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Wang Z, Chai C, Wang R, Feng Y, Huang L, Zhang Y, Xiao X, Yang S, Zhang Y, Zhang X. Single-cell transcriptome atlas of human mesenchymal stem cells exploring cellular heterogeneity. Clin Transl Med 2021; 11:e650. [PMID: 34965030 PMCID: PMC8715893 DOI: 10.1002/ctm2.650] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 10/24/2021] [Accepted: 10/30/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The heterogeneity of mesenchymal stem cells (MSCs) is poorly understood, thus limiting clinical application and basic research reproducibility. Advanced single-cell RNA sequencing (scRNA-seq) is a robust tool used to analyse for dissecting cellular heterogeneity. However, the comprehensive single-cell atlas for human MSCs has not been achieved. METHODS This study used massive parallel multiplexing scRNA-seq to construct an atlas of > 130 000 single-MSC transcriptomes across multiple tissues and donors to assess their heterogeneity. The most widely clinically utilised tissue resources for MSCs were collected, including normal bone marrow (n = 3), adipose (n = 3), umbilical cord (n = 2), and dermis (n = 3). RESULTS Seven tissue-specific and five conserved MSC subpopulations with distinct gene-expression signatures were identified from multiple tissue origins based on the high-quality data, which has not been achieved previously. This study showed that extracellular matrix (ECM) highly contributes to MSC heterogeneity. Notably, tissue-specific MSC subpopulations were substantially heterogeneous on ECM-associated immune regulation, antigen processing/presentation, and senescence, thus promoting inter-donor and intra-tissue heterogeneity. The variable dynamics of ECM-associated genes had discrete trajectory patterns across multiple tissues. Additionally, the conserved and tissue-specific transcriptomic-regulons and protein-protein interactions were identified, potentially representing common or tissue-specific MSC functional roles. Furthermore, the umbilical-cord-specific subpopulation possessed advantages in immunosuppressive properties. CONCLUSION In summary, this work provides timely and great insights into MSC heterogeneity at multiple levels. This MSC atlas taxonomy also provides a comprehensive understanding of cellular heterogeneity, thus revealing the potential improvements in MSC-based therapeutic efficacy.
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Affiliation(s)
- Zheng Wang
- Medical Center of Hematologythe Second Affiliated HospitalArmy Medical UniversityChongqingChina
- State Key Laboratory of TraumaBurn and Combined InjuryArmy Medical UniversityChongqingChina
| | - Chengyan Chai
- Medical Center of Hematologythe Second Affiliated HospitalArmy Medical UniversityChongqingChina
- State Key Laboratory of TraumaBurn and Combined InjuryArmy Medical UniversityChongqingChina
| | - Rui Wang
- Medical Center of Hematologythe Second Affiliated HospitalArmy Medical UniversityChongqingChina
- State Key Laboratory of TraumaBurn and Combined InjuryArmy Medical UniversityChongqingChina
| | - Yimei Feng
- Medical Center of Hematologythe Second Affiliated HospitalArmy Medical UniversityChongqingChina
- State Key Laboratory of TraumaBurn and Combined InjuryArmy Medical UniversityChongqingChina
| | - Lei Huang
- Department of Urologythe Second Affiliated HospitalArmy Military Medical UniversityChongqingChina
| | - Yiming Zhang
- Department of Plastic and Cosmetic Surgerythe Second Affiliated HospitalArmy Medical UniversityChongqingChina
| | - Xia Xiao
- Time Plastic Surgery HospitalChongqingChina
| | - Shijie Yang
- Medical Center of Hematologythe Second Affiliated HospitalArmy Medical UniversityChongqingChina
- State Key Laboratory of TraumaBurn and Combined InjuryArmy Medical UniversityChongqingChina
| | - Yunfang Zhang
- Medical Center of Hematologythe Second Affiliated HospitalArmy Medical UniversityChongqingChina
- State Key Laboratory of TraumaBurn and Combined InjuryArmy Medical UniversityChongqingChina
| | - Xi Zhang
- Medical Center of Hematologythe Second Affiliated HospitalArmy Medical UniversityChongqingChina
- State Key Laboratory of TraumaBurn and Combined InjuryArmy Medical UniversityChongqingChina
- National Clinical Research Center for Hematologic Diseasesthe First Affiliated Hospital of Soochow UniversitySuzhouChina
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Fatima A, Malick TS, Khan I, Ishaque A, Salim A. Effect of glycyrrhizic acid and 18β-glycyrrhetinic acid on the differentiation of human umbilical cord-mesenchymal stem cells into hepatocytes. World J Stem Cells 2021; 13:1580-1594. [PMID: 34786159 PMCID: PMC8567450 DOI: 10.4252/wjsc.v13.i10.1580] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/25/2021] [Accepted: 09/19/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND End-stage liver disease is a global health complication with high prevalence and limited treatment options. Cell-based therapies using mesenchymal stem cells (MSCs) emerged as an alternative approach to support hepatic regeneration. In vitro preconditioning strategies have been employed to strengthen the regenerative and differentiation potential of MSCs towards hepatic lineage. Chemical compounds of the triterpene class; glycyrrhizic acid (GA) and 18β-glycyrrhetinic acid (GT) possess diverse therapeutic properties including hepato-protection and anti-fibrosis characteristics. They are capable of modulating several signaling pathways that are crucial in hepatic regeneration. Preconditioning with hepato-protective triterpenes may stimulate MSC fate transition towards hepatocytes. AIM To explore the effect of GA and GT on hepatic differentiation of human umbilical cord-MSCs (hUC-MSCs). METHODS hUC-MSCs were isolated and characterized phenotypically by flow cytometry and immunocytochemistry for the expression of MSC-associated surface molecules. Isolated cells were treated with GA, GT, and their combination for 24 h and then analyzed at three time points; day 7, 14, and 21. qRT-PCR was performed for the expression of hepatic genes. Expression of hepatic proteins was analyzed by immunocytochemistry at day 21. Periodic acid Schiff staining was performed to determine the functional ability of treated cells. RESULTS The fusiform-shaped morphology of MSCs in the treatment groups in comparison with the untreated control, eventually progressed towards the polygonal morphology of hepatocytes with the passage of time. The temporal transcriptional profile of preconditioned MSCs displayed significant expression of hepatic genes with increasing time of differentiation. Preconditioned cells showed positive expression of hepatocyte-specific proteins. The results were further corroborated by positive periodic acid Schiff staining, indicating the presence of glycogen in their cytoplasm. Moreover, bi-nucleated cells, which is the typical feature of hepatocytes, were also seen in the preconditioned cells. CONCLUSION Preconditioning with glycyrrhizic acid, 18β-glycyrrhetinic acid and their combination, successfully differentiates hUC-MSCs into hepatic-like cells. These MSCs may serve as a better therapeutic option for degenerative liver diseases in future.
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Affiliation(s)
- Abiha Fatima
- Stem Cell Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Tuba Shakil Malick
- Stem Cell Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Irfan Khan
- Stem Cell Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Aisha Ishaque
- Stem Cell Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Asmat Salim
- Stem Cell Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi 75270, Sindh, Pakistan.
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Matheni C, Dsouza W. Xeno-Free Human Wharton's Jelly Mesenchymal Stromal Cells Maintain Their Characteristic Properties after Long-Term Cryopreservation. CELL JOURNAL 2021; 23:145-153. [PMID: 34096215 PMCID: PMC8181313 DOI: 10.22074/cellj.2021.7131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Accepted: 12/22/2019] [Indexed: 11/30/2022]
Abstract
Objective The past decade has witnessed a rapid growth in harnessing the potential of adult stem cells for regenerative
medicine. An investigational new drug (IND) or a regenerative medicine advanced therapy (RMAT) product must fulfil
many requirements, such as stability studies, after cryopreservation. Such studies are important to ascertain the utility
of off-the-shelf allogeneic cells for clinical applications. The present work describes a complete characterisation of xeno-
free human Wharton’s Jelly mesenchymal stromal cells (hWJ-MSCs) before and up to 28 months post-cryopreservation.
Materials and Methods In this experimental study, culture methods that involved plasma derived human serum and
recombinant trypsin were used to develop clinical grade cells. Complete cell characterisation involved flow cytometry
studies for viability, positive and negative markers, colony forming unit (CFU) potential, population doubling time (PDT),
soft agar assay to evaluate in vitro tumourigenicity, karyotype analysis and differentiation studies which were performed
before and at 6, 12, 18 and 28 months post-cryopreservation.
Results Our data showed consistency in the flow cytometry, CFU assay, PDT, soft agar assay, karyotyping and
differentiation studies.
Conclusion Using our protocols for extended xeno-free culture and cryopreservation of hWJ-MSCs, we could establish
the shelf life of the cell-based product for up to 28 months.
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Toyota A, Shinagawa R, Mano M, Tokioka K, Suda N. Regeneration in Experimental Alveolar Bone Defect Using Human Umbilical Cord Mesenchymal Stem Cells. Cell Transplant 2021; 30:963689720975391. [PMID: 33573392 PMCID: PMC7883160 DOI: 10.1177/0963689720975391] [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] [Indexed: 12/11/2022] Open
Abstract
Cleft lip and palate is a congenital disorder including cleft lip, and/or cleft palate, and/or alveolar cleft, with high incidence.The alveolar cleft causes morphological and functional abnormalities. To obtain bone bridge formation and continuous structure between alveolar clefts, surgical interventions are performed from infancy to childhood. However, desirable bone bridge formation is not obtained in many cases. Regenerative medicine using mesenchymal stem cells (MSCs) is expected to be a useful strategy to obtain sufficient bone bridge formation between alveolar clefts. In this study, we examined the effect of human umbilical cord-derived MSCs by transplantation into a rat experimental alveolar cleft model. Human umbilical cords were digested enzymatically and the isolated cells were collected (UC-EZ cells). Next, CD146-positive cells were enriched from UC-EZ cells by magnetic-activated cell sorting (UC-MACS cells). UC-EZ and UC-MACS cells showed MSC gene/protein expression, in vitro. Both cells had multipotency and could differentiate to osteogenic, chondrogenic, and adipogenic lineages under the differentiation-inducing media. However, UC-EZ cells lacked Sox2 expression and showed the lower ratio of MSCs than UC-MACS cells. Thus, UC-MACS cells were transplanted with hydroxyapatite and collagen (HA + Col) into alveolar cleft model to evaluate bone formation in vivo. The results of micro computed tomography and histological staining showed that UC-MACS cells with HA + Col induced more abundant bone formation between the experimental alveolar clefts than HA + Col implantation only. Cells immunopositive for osteopontin were accumulated along the bone surface and some of them were embedded in the bone. Cells immunopositive for human-specific mitochondria were aligned along the newly formed bone surface and in the new bone, suggesting that UC-MACS cells contributed to the bone bridge formation between alveolar clefts. These findings indicate that human umbilical cords are reliable bioresource and UC-MACS cells are useful for the alveolar cleft regeneration.
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Affiliation(s)
- Akiko Toyota
- Division of Orthodontics, Department of Human Development and Fostering, Meikai University School of Dentistry, Saitama, Japan
| | - Rei Shinagawa
- Division of Orthodontics, Department of Human Development and Fostering, Meikai University School of Dentistry, Saitama, Japan
| | - Mikiko Mano
- Division of Orthodontics, Department of Human Development and Fostering, Meikai University School of Dentistry, Saitama, Japan
| | - Kazuyuki Tokioka
- Department of Plastic and Reconstructive Surgery, Saitama Medical University, Saitama, Japan
| | - Naoto Suda
- Division of Orthodontics, Department of Human Development and Fostering, Meikai University School of Dentistry, Saitama, Japan
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11
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Silini AR, Di Pietro R, Lang-Olip I, Alviano F, Banerjee A, Basile M, Borutinskaite V, Eissner G, Gellhaus A, Giebel B, Huang YC, Janev A, Kreft ME, Kupper N, Abadía-Molina AC, Olivares EG, Pandolfi A, Papait A, Pozzobon M, Ruiz-Ruiz C, Soritau O, Susman S, Szukiewicz D, Weidinger A, Wolbank S, Huppertz B, Parolini O. Perinatal Derivatives: Where Do We Stand? A Roadmap of the Human Placenta and Consensus for Tissue and Cell Nomenclature. Front Bioeng Biotechnol 2020; 8:610544. [PMID: 33392174 PMCID: PMC7773933 DOI: 10.3389/fbioe.2020.610544] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 11/23/2020] [Indexed: 02/05/2023] Open
Abstract
Progress in the understanding of the biology of perinatal tissues has contributed to the breakthrough revelation of the therapeutic effects of perinatal derivatives (PnD), namely birth-associated tissues, cells, and secreted factors. The significant knowledge acquired in the past two decades, along with the increasing interest in perinatal derivatives, fuels an urgent need for the precise identification of PnD and the establishment of updated consensus criteria policies for their characterization. The aim of this review is not to go into detail on preclinical or clinical trials, but rather we address specific issues that are relevant for the definition/characterization of perinatal cells, starting from an understanding of the development of the human placenta, its structure, and the different cell populations that can be isolated from the different perinatal tissues. We describe where the cells are located within the placenta and their cell morphology and phenotype. We also propose nomenclature for the cell populations and derivatives discussed herein. This review is a joint effort from the COST SPRINT Action (CA17116), which broadly aims at approaching consensus for different aspects of PnD research, such as providing inputs for future standards for the processing and in vitro characterization and clinical application of PnD.
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Affiliation(s)
- Antonietta Rosa Silini
- Centro di Ricerca E. Menni, Fondazione Poliambulanza-Istituto Ospedaliero, Brescia, Italy
| | - Roberta Di Pietro
- Department of Medicine and Ageing Sciences, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
- StemTeCh Group, G. d’Annunzio Foundation, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
| | - Ingrid Lang-Olip
- Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria
| | - Francesco Alviano
- Department of Experimental, Diagnostic and Specialty Medicine, Unit of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy
| | - Asmita Banerjee
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Mariangela Basile
- Department of Medicine and Ageing Sciences, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
- StemTeCh Group, G. d’Annunzio Foundation, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
| | - Veronika Borutinskaite
- Department of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | - Günther Eissner
- Systems Biology Ireland, School of Medicine, University College Dublin, Dublin, Ireland
| | - Alexandra Gellhaus
- Department of Gynecology and Obstetrics, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Bernd Giebel
- Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Yong-Can Huang
- Shenzhen Engineering Laboratory of Orthopaedic Regenerative Technologies, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, China
| | - Aleksandar Janev
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Mateja Erdani Kreft
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Nadja Kupper
- Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria
| | - Ana Clara Abadía-Molina
- Instituto de Biopatología y Medicina Regenerativa, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain
- Departamento de Bioquímica y Biología Molecular III e Inmunología, Universidad de Granada, Granada, Spain
| | - Enrique G. Olivares
- Instituto de Biopatología y Medicina Regenerativa, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain
- Departamento de Bioquímica y Biología Molecular III e Inmunología, Universidad de Granada, Granada, Spain
- Unidad de Gestión Clínica Laboratorios, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | - Assunta Pandolfi
- StemTeCh Group, G. d’Annunzio Foundation, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
- Vascular and Stem Cell Biology, Department of Medical, Oral and Biotechnological Sciences, G. d’Annunzio University of Chieti-Pescara, CAST (Center for Advanced Studies and Technology, ex CeSI-MeT), Chieti, Italy
| | - Andrea Papait
- Centro di Ricerca E. Menni, Fondazione Poliambulanza-Istituto Ospedaliero, Brescia, Italy
- Department of Life Science and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Michela Pozzobon
- Stem Cells and Regenerative Medicine Lab, Department of Women’s and Children’s Health, University of Padova, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, Italy
| | - Carmen Ruiz-Ruiz
- Instituto de Biopatología y Medicina Regenerativa, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain
- Departamento de Bioquímica y Biología Molecular III e Inmunología, Universidad de Granada, Granada, Spain
| | - Olga Soritau
- The Oncology Institute “Prof. Dr. Ion Chiricuta”, Cluj-Napoca, Romania
| | - Sergiu Susman
- Department of Morphological Sciences-Histology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Department of Pathology, IMOGEN Research Center, Cluj-Napoca, Romania
| | - Dariusz Szukiewicz
- Department of General and Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, Warsaw, Poland
| | - Adelheid Weidinger
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Susanne Wolbank
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Berthold Huppertz
- Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria
| | - Ornella Parolini
- Department of Life Science and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy
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12
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Yigman Z, Ozdemir ED, Turan NN, Ulus AT, Can A. Umbilical cord mesenchymal stromal cells engraft and transdifferentiate into cardiomyocyte-like cells following acute myocardial ischemia⋆. Acta Histochem 2020; 122:151578. [PMID: 32778240 DOI: 10.1016/j.acthis.2020.151578] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 06/17/2020] [Accepted: 06/19/2020] [Indexed: 01/14/2023]
Abstract
OBJECTIVE Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) gained importance in acute/chronic ischemic cardiomyopathy because of their outstanding regenerative potential in various pathologic conditions. The present study was designed to determine to what extent hUC-MSCs contribute to myocardial regeneration in acute experimental myocardial infarction (MI) in rats. METHODS Animals were assigned into two groups; the control group received intramyocardial PBS injections, while the hUC-MSC group received calcein-AM-labeled 8.8 × 106/kg hUC-MSCs. Three weeks following the acute MI induction, rats were sacrificed after assessing the left ventricular (LV) function using echocardiography. For the assessment of infarct size, the triphenyl tetrazolium chloride (TTC) test was used in isolated hearts. Collagen-rich scar tissue was demonstrated using Masson's trichrome staining, followed by the detection of cardiac troponin I (cTnI), α-sarcomeric actin (α-SA), von Willebrand factor (vWF), CD68 and CD206 expressions in control and cell-injected sections. RESULTS Echocardiography revealed a significant difference (P = 0.037) in the LV ejection fraction between groups. TTC assays demonstrated a significant difference (P = 0.006) between the groups regarding the ratio of the infarcted LV area. Calcein-AM-loaded cells were identified mostly in ischemic myocardium. Transplanted cells also expressed human-specific cTnI, providing concrete proof of transdifferentiation into cardiomyocytes, and α-SA. vWF+ cells verified the neovascularization in the ischemic myocardium. Finally, a slight shift from pro-inflammatory to anti-inflammatory macrophages (CD68+/CD206+) was noted in both groups. CONCLUSIONS We found that the intramyocardial transplanted hUC-MSCs engrafted and partially transdifferentiated into cardiomyocytes, reduced scar formation, and induced angiogenesis through the association of pro/anti-inflammatory macrophages.
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Affiliation(s)
- Zeynep Yigman
- Gazi University Faculty of Medicine, Department of Histology and Embryology, Yenimahalle, Ankara, 06560, Turkey.
| | - Elif Derya Ozdemir
- Gazi University Faculty of Pharmacy, Department of Pharmacology, Yenimahalle, Ankara, 06560, Turkey.
| | - Nilufer N Turan
- Cardiovascular Research Center, Division of Cardiology, Rhode Island Hospital, Warren Alpert School of Brown University, Providence, RI, 02903, USA.
| | - A Tulga Ulus
- Hacettepe University Faculty of Medicine, Department of Cardiovascular and Thoracic Surgery, Sihhiye, Ankara, 06100, Turkey.
| | - Alp Can
- Ankara University School of Medicine, Department of Histology and Embryology, Laboratories for Stem Cells and Reproductive Medicine, Sihhiye, Ankara, 06100, Turkey.
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13
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Can A, Coskun H. The rationale of using mesenchymal stem cells in patients with COVID-19-related acute respiratory distress syndrome: What to expect. Stem Cells Transl Med 2020; 9:1287-1302. [PMID: 32779878 PMCID: PMC7404450 DOI: 10.1002/sctm.20-0164] [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: 04/17/2020] [Revised: 06/06/2020] [Accepted: 06/23/2020] [Indexed: 02/06/2023] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐caused coronavirus disease 2019 (COVID‐19) pandemic has become a global health crisis with an extremely rapid progress resulting in thousands of patients who may develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) treatment. So far, no specific antiviral therapeutic agent has been demonstrated to be effective for COVID‐19; therefore, the clinical management is largely supportive and depends on the patients' immune response leading to a cytokine storm followed by lung edema, dysfunction of air exchange, and ARDS, which could lead to multiorgan failure and death. Given that human mesenchymal stem cells (MSCs) from various tissue sources have revealed successful clinical outcomes in many immunocompromised disorders by inhibiting the overactivation of the immune system and promoting endogenous repair by improving the microenvironment, there is a growing demand for MSC infusions in patients with COVID‐19‐related ARDS in the ICU. In this review, we have documented the rationale and possible outcomes of compassionate use of MSCs, particularly in patients with SARS‐CoV‐2 infections, toward proving or disproving the efficacy of this approach in the near future. Many centers have registered and approved, and some already started, single‐case or phase I/II trials primarily aiming to rescue their critical patients when no other therapeutic approach responds. On the other hand, it is also very important to mention that there is a good deal of concern about clinics offering unproven stem cell treatments for COVID‐19. The reviewers and oversight bodies will be looking for a balanced but critical appraisal of current trials.
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Affiliation(s)
- Alp Can
- Laboratory for Stem Cells and Reproductive Cell Biology, Department of Histology and Embryology, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Hakan Coskun
- Harvard Medical School, Boston, Massachusetts, USA.,Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA
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14
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PFA is superior to glyoxal in preserving oocyte, embryo, and stem cell proteins evidenced by super-resolution microscopical surveys of epitopes. J Assist Reprod Genet 2020; 37:369-384. [PMID: 31930433 DOI: 10.1007/s10815-019-01666-9] [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: 10/24/2019] [Accepted: 12/12/2019] [Indexed: 10/25/2022] Open
Abstract
PURPOSE Chemical fixation is a critical step to retaining cellular targets as naturally as possible. Recent developments in microscopy allow sophisticated detection and measuring techniques with which spatio-temporal molecular alterations are conceivable. In this study, we compare two members of aldehyde fixatives [i.e., glyoxal (Gly) and paraformaldehyde (PFA)] to determine whether Gly, a less toxic dialdehyde fixative that is considered to retain immunoreactivity could provide a successful and consistent cell fixation in favor of PFA in various cell preparations and types. METHODS We document the fixation competence of Gly and PFA side-by-side (with or without Triton X-100 permeabilization) in live- and fixed-cell preparations in mouse oocytes, embryos, and human somatic cells (human umbilical cord-derived mesenchymal stromal cells) using protein quantification by Western blot assay and super-resolution microscopy. RESULTS Although Gly seemed to act faster than PFA, catastrophic consequences were found not acceptable, especially in oocytes and embryos. Due to cell lysate and immunocytochemistry surveys, it was obvious that PFA is superior to Gly in retaining cellular proteins in situ with little/no background staining. In many samples, PFA revealed more reliable and consistent results regarding the protein quantity and cellular localization corresponding to previously defined patterns in the literature. CONCLUSION Although the use of Gly is beneficial as indicated by previous reports, we concluded that it does not meet the requirement for proper fixation, at least for the tested cell types and proteins. However, PFA alone with no addition of TX displayed a significant cytoplasmic loss by generating membrane blebs during fixation.
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15
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Lu Q, El-Hashash AHK. Cell-based therapy for idiopathic pulmonary fibrosis. Stem Cell Investig 2019; 6:22. [PMID: 31559309 PMCID: PMC6737434 DOI: 10.21037/sci.2019.06.09] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Accepted: 06/18/2019] [Indexed: 12/22/2022]
Abstract
Idiopathic pulmonary fibrosis (IPF) is an example of interstitial lung diseases that is characterized by chronic, progressive, and fibrotic lung injuries. During lung fibrosis, normal healthy lung tissues are replaced by remarkably destroyed alveolar architecture and altered extracellular cell matrix. These changes eventually cause severe disruption of the tightly-controlled gas exchange process and reduction of lung compliance that ultimately lead to both respiratory failure and death. In the last decade, progress has been made toward understanding the pathogenesis of pulmonary fibrosis, and two novel disease-modifying therapies were approved. However, finding more effective treatments for pulmonary fibrosis is still a challenge, with its incidence continues to increase globally, which is associated with significantly high mortality, morbidity and economical healthcare burden. Different stem cell types have recently emerged as a promising therapy for human diseases, including lung fibrosis, with numerous studies on the identification, characterization, proliferation and differentiation of stem cells. A large body of both basic and pre-clinical research on stem cells has been recently translated to patient care worldwide. Herein, we review recent advances in our understanding of the pathophysiology of IPF, and types of cells used in IPF cell-based therapies, including alveolar and mixed lung epithelial cells, different stem cell types (MSCs, ADSCs, IPSCs…etc.), endogenous lung tissue-specific stem cells, and circulating endothelial progenitors (EPCs). We also discuss recent studies on the applications of these cells in IPF therapy and their delivery routes, effective doses for cell therapy, and timing of delivery. Finally, we discuss attractive recent and current clinical trials conducted on cell-based therapy for IPF.
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Affiliation(s)
- Qi Lu
- The University of Edinburgh-Zhejiang International campus (UoE-ZJU Institute), Haining, China
- Centre of Stem Cell and Regenerative Medicine Schools of Medicine & Basic Medicine, Hangzhou, China
| | - Ahmed H. K. El-Hashash
- The University of Edinburgh-Zhejiang International campus (UoE-ZJU Institute), Haining, China
- Centre of Stem Cell and Regenerative Medicine Schools of Medicine & Basic Medicine, Hangzhou, China
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16
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Celikkan FT, Mungan C, Sucu M, Ulus AT, Cinar O, Ili EG, Can A. Optimizing the transport and storage conditions of current Good Manufacturing Practice -grade human umbilical cord mesenchymal stromal cells for transplantation (HUC-HEART Trial). Cytotherapy 2018; 21:64-75. [PMID: 30455106 DOI: 10.1016/j.jcyt.2018.10.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 10/01/2018] [Accepted: 10/13/2018] [Indexed: 01/12/2023]
Abstract
BACKGROUND The HUC-HEART Trial is a clinical study of intramyocardial delivery of current Good Manufacturing Practice (cGMP)-grade human umbilical cord multipotent stromal cells (HUC-MSCs) in ischemic cardiomyopathy where 2 × 107 cells are administered to peri-infarcted myocardium. Prior to the onset of the trial, we aimed to optimize the transport/storage conditions for obtaining the highest cell viability and proliferation rate of cells to be transplanted. METHODS Cells were tested after being transported in phosphate-buffered saline (PBS) or Ringer's lactate-based (RL) transport media supplemented with human serum albumin (HSA) and/or hydroxyethyl starch (HES) at two temperatures (2-10°C or 22-24°C). RESULTS The effects of transport conditions on cell viability following 6 h were found highest (93.4 ± 1.5) in RL-based media at 2-10°C. Karyotypes were found normal upon transportation in any of the formulations and temperatures. However, the highest proliferation rate was noted (3.1-fold increase) in RL (1% HSA) media at 2-10°C over 6 days in culture. From that point, RL (1% HSA) media at 2-10°C was used for further experiments. The maximum cell storage time was detected around 24 h at 2-10°C. Extended storage periods resulted in a decrease in cell viability but not in MSC marker expression. An increase in actin quantity was detected in hypoxia (5% O2) groups in early culture days; no difference was noted between hypoxic versus normoxic (21% O2) conditions in later days. DISCUSSION The overall results suggest that non-commercial, simple media formulations with extended storage intervals at 2-10°C temperatures are capable of retaining the characteristics of clinical-grade HUC-MSCs. The above findings led us to use RL (1% HSA) media at 2-10°C for transport and storage in the HUC-HEART Trial; 23 patients received HUC-MSCs by August 2018; no adverse effects were noted related to cell processing and transplantation.
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Affiliation(s)
- Ferda Topal Celikkan
- Department of Histology and Embryology, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Ceren Mungan
- Ankara University Biotechnology Institute, Ankara, Turkey
| | - Merve Sucu
- Ankara University Biotechnology Institute, Ankara, Turkey
| | - A Tulga Ulus
- Division of Cardiovascular Surgery, Acibadem Hospital, Ankara, Turkey
| | - Ozgur Cinar
- Department of Histology and Embryology, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Ezgi Gokpinar Ili
- Department of Medical Genetics, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Alp Can
- Department of Histology and Embryology, Faculty of Medicine, Ankara University, Ankara, Turkey.
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Tong J, Yu Q, Xu W, Yu W, Wu C, Wu Y, Yan H. Montelukast enhances cytocidal effects of carfilzomib in multiple myeloma by inhibiting mTOR pathway. Cancer Biol Ther 2018; 20:381-390. [PMID: 30359543 DOI: 10.1080/15384047.2018.1529112] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Montelukast is an anti-asthmatic medication, and has recently showed its inhibitory effects on the proliferation of cancers. The purpose of this study was to identify the cytotoxic effects of montelukast on multiple myeloma (MM) cells and the combination effects of montelukast and carfilzomib in the treatment of MM. Results revealed that montelukast induced a dose- and time-dependent cytotoxicity in MM cells lines and significantly suppressed the colony formation of myeloma cells. Furthermore, montelukast enhanced the cytotoxicity of carfilzomib in MM cell lines. This anti-tumor effect was associated with decreased c-Myc via the inhibition of mTOR signaling pathway. Moreover, the combination of montelukast and carfilzomib induced apoptosis of myeloma cells effectively, even in the presence of bone marrow stromal cells (BMSCs). It is more important to note that the co-treatment exhibited similar cytocidal effects in carfilzomib-resistant cell lines (U266R and 8226R). In addition, the combined effects were noted in two MM xenograft mice models and 7 cases of human CD138+ myeloma cells (4 newly diagnosed cases and 3 relapsed cases) with no cytotoxicity on peripheral blood mononuclear cells (PBMCs) from 5 healthy donors. Our data suggested that montelukast enhanced the cytotoxicity of carfilzomib in both carfilzomib-sensitive and carfilzomib-resistant MM cell lines. These findings may facilitate the development of therapeutic strategies and provide a promising therapeutic combination regimen for the treatment of refractory myeloma.
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Affiliation(s)
- Jia Tong
- a Department of Hematology , Affiliated Rui-Jin Hospital of Shanghai Jiao-Tong University School of Medicine , Shanghai , China
| | - Qing Yu
- a Department of Hematology , Affiliated Rui-Jin Hospital of Shanghai Jiao-Tong University School of Medicine , Shanghai , China
| | - Wenbin Xu
- a Department of Hematology , Affiliated Rui-Jin Hospital of Shanghai Jiao-Tong University School of Medicine , Shanghai , China
| | - Wenjun Yu
- a Department of Hematology , Affiliated Rui-Jin Hospital of Shanghai Jiao-Tong University School of Medicine , Shanghai , China
| | - Chao Wu
- a Department of Hematology , Affiliated Rui-Jin Hospital of Shanghai Jiao-Tong University School of Medicine , Shanghai , China
| | - Yingli Wu
- b Hongqiao International Institute of Medicine, Shanghai Tongren Hospital; Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education , Shanghai Jiao Tong University School of Medicine , Shanghai , China
| | - Hua Yan
- a Department of Hematology , Affiliated Rui-Jin Hospital of Shanghai Jiao-Tong University School of Medicine , Shanghai , China
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18
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Ozkan S, Isildar B, Oncul M, Baslar Z, Kaleli S, Koyuturk M. Ultrastructural analysis of human umbilical cord derived MSCs at undifferentiated stage and during osteogenic and adipogenic differentiation. Ultrastruct Pathol 2018; 42:199-210. [PMID: 29624114 DOI: 10.1080/01913123.2018.1453905] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Mesenchymal stem cells (MSCs) are considered as an important tool for regenerative medicine and experimental treatments. Unveiling the ultrastructural changes during the differentiation of MSCs might help us to understand the nature of the process and to develop novel therapeutic approaches. For this purpose, human umbilical cord (hUC) was chosen as MSC source. In the first place, MSCs were isolated from sub-amniotic, intervascular and perivascular areas of hUC by enzymatic and tissue explant method to determine the most favorable region of hUC and technique for further processing. Therefore, microscopic and growth kinetics analyses showed that there was no clear difference in the morphologies and proliferation rates among the hUC-MSC groups. Flow cytometric analysis showed that CD44 and CD90 MSC markers were highly expressed, while CD34 and CD45 hematopoietic stem cells markers were expressed at low degree. Because our preliminary results showed that there was no conspicuous superiority among the hUC-MSCs groups, whole UC was utilized as a source, and tissue explant method was applied to isolate MSCs for further differentiation analysis. At the 1st and 3rd week of osteogenic and adipogenic differentiation, ultrastructural analysis showed an increase in the number of secondary lysosomes in comparison with the undifferentiated status. Increase in the mitochondrial content was also detected at the 1st week of adipogenic differentiation. Consequently, ultrastructural changes including increase in the number of mitochondria and secondary lysosomes during the adipogenic and osteogenic differentiation could be attributed to the switch in energy metabolism of the MSCs and increment in the lysosomal activity respectively.
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Affiliation(s)
- Serbay Ozkan
- a Department of Histology and Embryology, Cerrahpasa Medical Faculty , Istanbul University , Istanbul , Turkey
| | - Basak Isildar
- a Department of Histology and Embryology, Cerrahpasa Medical Faculty , Istanbul University , Istanbul , Turkey
| | - Mahmut Oncul
- b Department of Obstetrics and Gynecology, Cerrahpasa Medical Faculty , Istanbul University , Istanbul , Turkey
| | - Zafer Baslar
- c Division of Hematology, Department of Internal Medicine, Cerrahpasa Medical Faculty , Istanbul University , Istanbul , Turkey
| | - Semih Kaleli
- b Department of Obstetrics and Gynecology, Cerrahpasa Medical Faculty , Istanbul University , Istanbul , Turkey
| | - Meral Koyuturk
- a Department of Histology and Embryology, Cerrahpasa Medical Faculty , Istanbul University , Istanbul , Turkey
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Therapeutic Application of Human Wharton Jelly Mesenchymal Stem Cells in Skin Injury of SCID. Methods Mol Biol 2018; 1553:115-132. [PMID: 28229411 DOI: 10.1007/978-1-4939-6756-8_9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Mesenchymal stem cells (MSCs) are blossoming as a credible source for regenerative medical applications. The use of fetal MSCs is gaining momentum for therapeutic use. The ease of isolation, enhanced characteristics, and immunomodulation properties renders the utilization of fetal MSCs for numerous clinical applications. In this article, we will demonstrate a step-by-step protocol for isolation of Wharton's jelly MSCs (WJMSCs) from the human umbilical cord matrix, preparation of human platelet lysate, fabricating amniotic membrane scaffold and mice model to study skin regeneration using a combination of MSCs and decellularized amniotic membrane scaffold.
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Clinical-grade human umbilical cord-derived mesenchymal stem cells reverse cognitive aging via improving synaptic plasticity and endogenous neurogenesis. Cell Death Dis 2017; 8:e2996. [PMID: 28796260 PMCID: PMC5596535 DOI: 10.1038/cddis.2017.316] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 05/17/2017] [Accepted: 05/23/2017] [Indexed: 12/14/2022]
Abstract
Cognitive aging is a leading public health concern with the increasing aging population, but there is still lack of specific interventions directed against it. Recent studies have shown that cognitive function is intimately affected by systemic milieu in aging brain, and improvement of systemic environment in aging brain may be a promising approach for rejuvenating cognitive aging. Here, we sought to study the intervention effects of clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on cognitive aging in a murine model of aging. The conventional aging model in mice induced by d-galactose (d-gal) was employed here. Mice received once every two weeks intraperitoneal administration of hUC-MSCs. After 3 months of systematical regulation of hUC-MSCs, the hippocampal-dependent learning and memory ability was effectively improved in aged mice, and the synaptic plasticity was remarkably enhanced in CA1 area of the aged hippocampus; moreover, the neurobiological substrates that could impact on the function of hippocampal circuits were recovered in the aged hippocampus reflecting in: dendritic spine density enhanced, neural sheath and cytoskeleton restored, and postsynaptic density area increased. In addition, the activation of the endogenic neurogenesis which is beneficial to stabilize the neural network in hippocampus was observed after hUC-MSCs transplantation. Furthermore, we demonstrated that beneficial effects of systematical regulation of hUC-MSCs could be mediated by activation of mitogen-activated protein kinase (MAPK)-ERK-CREB signaling pathway in the aged hippocampus. Our study provides the first evidence that hUC-MSCs, which have the capacity of systematically regulating the aging brain, may be a potential intervention for cognitive aging.
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Xiang RF, Wang Y, Zhang N, Xu WB, Cao Y, Tong J, Li JM, Wu YL, Yan H. MK2206 enhances the cytocidal effects of bufalin in multiple myeloma by inhibiting the AKT/mTOR pathway. Cell Death Dis 2017; 8:e2776. [PMID: 28492559 PMCID: PMC5520709 DOI: 10.1038/cddis.2017.188] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 03/10/2017] [Accepted: 03/21/2017] [Indexed: 02/08/2023]
Abstract
Despite the development of promising cancer therapeutic drugs, multiple myeloma (MM) remains an incurable disease. Bufalin is a bufanolide steroid compound of the traditional Chinese medicine Chan Su that was previously shown to exert growth suppression effects on myeloma cell lines. Previous studies conducted by our group demonstrated that bufalin activated the AKT/mTOR pathway in myeloma cells, which is considered an essential pathway to disease progression and is related to drug resistance in MM. In view of the significant role of AKT in MM, the allosteric AKT inhibitor MK2206 was selected in order to enhance the antitumor effects of bufalin in different MM cell lines (NCI-H929, U266, LP-1 and RPMI8226). The data indicated that MK2206 enhanced the cytotoxicity of bufalin in MM cells, via the suppression of cellular proliferation and the induction of apoptosis, as demonstrated by cleavage of apoptosis-related proteins. This effect was further noted in the presence of exogenous interleukin-6 and/or following the co-culture of MM cells with bone marrow stromal cells (BMSC). This process was associated with the inhibition of the AKT/mTOR pathway. The combination of bufalin with MK2206 reduced the secretion of IL-6 in U266 cells. The combined treatment exhibited similar anti-MM effects in bortezomib-resistant cell lines (NCI-H929R, U266R). In addition to the in vitro cell line models, the synergistic effect was noted in primary MM cells and in MM xenografts of BALB-c and NOD-SCID mice. In conclusion, the data suggested that MK2206 significantly enhanced the cytocidal effects of bufalin in MM cells, regardless of the sensitivity to bortezomib, via the inhibition of the AKT/mTOR pathway. The study provided the basis of a promising treatment approach for MM.
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Affiliation(s)
- Ru-Fang Xiang
- Department of Hematology, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - Yan Wang
- Department of Hematology, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - Nan Zhang
- Department of Hematology, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - Wen-Bin Xu
- Department of Hematology, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - Yang Cao
- Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China
| | - Jia Tong
- Department of Hematology, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - Jun-Min Li
- Department of Hematology, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - Ying-Li Wu
- Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Hua Yan
- Department of Hematology, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
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Using Stem Cells to Grow Artificial Tissue for Peripheral Nerve Repair. Stem Cells Int 2016; 2016:7502178. [PMID: 27212954 PMCID: PMC4861803 DOI: 10.1155/2016/7502178] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Revised: 02/17/2016] [Accepted: 03/02/2016] [Indexed: 12/17/2022] Open
Abstract
Peripheral nerve injury continues to pose a clinical hurdle despite its frequency and advances in treatment. Unlike the central nervous system, neurons of the peripheral nervous system have a greater ability to regenerate. However, due to a number of confounding factors, this is often both incomplete and inadequate. The lack of supportive Schwann cells or their inability to maintain a regenerative phenotype is a major factor. Advances in nervous system tissue engineering technology have led to efforts to build Schwann cell scaffolds to overcome this and enhance the regenerative capacity of neurons following injury. Stem cells that can differentiate along a neural lineage represent an essential resource and starting material for this process. In this review, we discuss the different stem cell types that are showing promise for nervous system tissue engineering in the context of peripheral nerve injury. We also discuss some of the biological, practical, ethical, and commercial considerations in using these different stem cells for future clinical application.
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Subramani B, Subbannagounder S, Palanivel S, Ramanathanpullai C, Sivalingam S, Yakub A, SadanandaRao M, Seenichamy A, Pandurangan AK, Tan JJ, Ramasamy R. Generation and characterization of human cardiac resident and non-resident mesenchymal stem cell. Cytotechnology 2016; 68:2061-73. [PMID: 26820972 DOI: 10.1007/s10616-016-9946-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Accepted: 01/14/2016] [Indexed: 01/14/2023] Open
Abstract
Despite the surgical and other insertional interventions, the complete recuperation of myocardial disorders is still elusive due to the insufficiency of functioning myocardiocytes. Thus, the use of stem cells to regenerate the affected region of heart becomes a prime important. In line with this human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have gained considerable interest due to their potential use for mesodermal cell based replacement therapy and tissue engineering. Since MSCs are harvested from various organs and anatomical locations of same organism, thus the cardiac regenerative potential of human cardiac-derived MSCs (hC-MSCs) and human umbilical cord Wharton's Jelly derived MSC (hUC-MSCs) were tested concurrently. At in vitro culture, both hUC-MSCs and hC-MSCs assumed spindle shape morphology with expression of typical MSC markers namely CD105, CD73, CD90 and CD44. Although, hUC-MSCs and hC-MSCs are identical in term of morphology and immunophenotype, yet hUC-MSCs harbored a higher cell growth as compared to the hC-MSCs. The inherent cardiac regenerative potential of both cells were further investigated with mRNA expression of ion channels. The RT-PCR results demonstrated that both MSCs were expressing a notable level of delayed rectifier-like K(+) current (I KDR ) ion channel, yet the relative expression level was considerably varied between hUC-MSCs and hC-MSCs that Kv1.1(39 ± 0.6 vs 31 ± 0.8), Kv2.1 (6 ± 0.2 vs 21 ± 0.12), Kv1.5 (7.4 ± 0.1 vs 6.8 ± 0.06) and Kv7.3 (27 ± 0.8 vs 13.8 ± 0.6). Similarly, the Ca2(+)-activated K(+) current (I KCa ) channel encoding gene, transient outward K(+) current (I to ) and TTX-sensitive transient inward sodium current (I Na.TTX ) encoding gene (Kv4.2, Kv4.3 and hNE-Na) expressions were detected in both groups as well. Despite the morphological and phenotypical similarity, the present study also confirms the existence of multiple functional ion channel currents IKDR, IKCa, Ito, and INa.TTX in undifferentiated hUC-MSCs as of hC-MSCs. Thus, the hUC-MSCs can be exploited as a potential candidate for future cardiac regeneration.
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Affiliation(s)
- Baskar Subramani
- Nichi-Asia Life Sdn Bhd., 47810, Petaling Jaya, Selangor, Malaysia
- Bharathiyar University, Coimbatore, Tamil Nadu, India
| | | | - Sekar Palanivel
- Departments of Zoology, Government Arts College (Autonomous), Salem, 636007, Tamil Nadu, India
| | | | - Sivakumar Sivalingam
- Cardiothoracic Surgery Unit, National Heart Institute, 50400, Kuala Lumpur, Malaysia
| | - Azhari Yakub
- Cardiothoracic Surgery Unit, National Heart Institute, 50400, Kuala Lumpur, Malaysia
| | | | - Arivudainambi Seenichamy
- Department of Veterinary Pathology and Microbiology, Universiti Putra Malaysia, Serdang, Malaysia
| | - Ashok Kumar Pandurangan
- Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Jun Jie Tan
- Regeneration Medicine Cluster, Advanced Medicine and Dental Institute, Universiti Sains Malaysia, George Town, Pulau Pinang, Malaysia
| | - Rajesh Ramasamy
- Stem Cell and Immunity Group, Immunology Laboratory Unit, Department Of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
- Stem Cell Research Laboratory, Genetic and Regenerative Medicine Research Center, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
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Ghadiri M, Young PM, Traini D. Cell-based therapies for the treatment of idiopathic pulmonary fibrosis (IPF) disease. Expert Opin Biol Ther 2015; 16:375-87. [PMID: 26593230 DOI: 10.1517/14712598.2016.1124085] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
INTRODUCTION During the last few decades, cell-based therapies have shown great potential to treat patients with lung diseases. It has been proposed that the administration of cells into an injured lung could be considered as a therapeutic method to repair and replace lost lung tissue. Using this method, transplanted cells with the ability to proliferate and differentiate into alveolar cells, have been suggested as a therapeutic strategy for IPF treatment. AREAS COVERED In this review, the latest investigations using various types of cells for IPF therapy have been presented. The cells studied for cell-based therapies in IPF are lung alveolar epithelial cells, lung resident stem cells and exogenous adult stem cells such as MSCs. EXPERT OPINION After many years of investigation, the use of cell-based therapies to treat IPF is still at the experimental phase. Problems include bioethical issues, safety of cell transplantation, routes of delivery and the dose and timing of administration. Further investigations are necessary to establish the best strategy for using cell-based therapies effectively for the treatment of IPF.
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Affiliation(s)
- Maliheh Ghadiri
- a Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology , Sydney Medical School , Sydney , NSW , Australia
| | - Paul M Young
- a Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology , Sydney Medical School , Sydney , NSW , Australia
| | - Daniela Traini
- a Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology , Sydney Medical School , Sydney , NSW , Australia
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Mehrpour SR, Mobasseri A, Amoozgar B. Mesenchymal stem cells injection with core decompression in the treatment of Kienbock disease. JOURNAL OF MEDICAL HYPOTHESES AND IDEAS 2015. [DOI: 10.1016/j.jmhi.2015.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Li H, Li T, Fan J, Li T, Fan L, Wang S, Weng X, Han Q, Zhao RC. miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K/AKT pathway. Cell Death Differ 2015. [PMID: 26206089 DOI: 10.1038/cdd.2015.99] [Citation(s) in RCA: 117] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Osteoporosis is a disease marked by reduced bone mass, leading to an increased risk of fractures or broken bones. Bone formation is mediated by recruiting mesenchymal stem cells (MSCs). Elucidation of the molecular mechanisms that regulate MSC differentiation into osteoblasts is of great importance for the development of anabolic therapies for osteoporosis and other bone metabolism-related diseases. microRNAs (miRNAs) have been reported to have crucial roles in bone development, osteogenic differentiation and osteoporosis pathophysiology. However, to date, only a few miRNAs have been reported to enhance osteogenesis and regulate the suppressive effect of glucocorticoids on osteogenic differentiation. In this study, we discovered that miR-216a, a pancreatic-specific miRNA, was significantly upregulated during osteogenic differentiation in human adipose-derived MSCs (hAMSCs). The expression of miR-216a was positively correlated with the expression of bone formation marker genes in clinical osteoporosis samples. Functional analysis demonstrated that miR-216a can markedly promote osteogenic differentiation of hAMSCs, rescue the suppressive effect of dexamethasone (DEX) on osteogenic differentiation in vitro and enhance bone formation in vivo. c-Cbl, a gene that encodes a RING finger E3 ubiquitin ligase, was identified as a direct target of miR-216a. Downregulation of c-Cbl by short hairpin RNAs can mimic the promotion effects of miR-216a and significantly rescue the suppressive effects of DEX on osteogenesis. Pathway analysis indicated that miR-216a regulation of osteogenic differentiation occurs via the c-Cbl-mediated phosphatidylinositol 3 kinase (PI3K)/AKT pathway. The recovery effects of miR-216a on the inhibition of osteogenesis by DEX were attenuated after blocking the PI3K pathway. Thus, our findings suggest that miR-216a may serve as a novel therapeutic agent for the prevention and treatment of osteoporosis and other bone metabolism-related diseases.
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Affiliation(s)
- H Li
- Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing, China
| | - T Li
- Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing, China
| | - J Fan
- Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing, China
| | - T Li
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, 100730, China
| | - L Fan
- Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing, China
| | - S Wang
- Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing, China
| | - X Weng
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, 100730, China
| | - Q Han
- Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing, China
| | - R C Zhao
- Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing, China
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Noninvasive Optical Imaging and In Vivo Cell Tracking of Indocyanine Green Labeled Human Stem Cells Transplanted at Superficial or In-Depth Tissue of SCID Mice. Stem Cells Int 2015; 2015:606415. [PMID: 26240573 PMCID: PMC4512618 DOI: 10.1155/2015/606415] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Revised: 03/12/2015] [Accepted: 03/23/2015] [Indexed: 12/11/2022] Open
Abstract
Stem cell based therapies hold great promise for the treatment of human diseases; however results from several recent clinical studies have not shown a level of efficacy required for their use as a first-line therapy, because more often in these studies fate of the transplanted cells is unknown. Thus monitoring the real-time fate of in vivo transplanted cells is essential to validate the full potential of stem cells based therapy. Recent studies have shown how real-time in vivo molecular imaging has helped in identifying hurdles towards clinical translation and designing potential strategies that may contribute to successful transplantation of stem cells and improved outcomes. At present, there are no cost effective and efficient labeling techniques for tracking the cells under in vivo conditions. Indocyanine green (ICG) is a safer, economical, and superior labelling technique for in vivo optical imaging. ICG is a FDA-approved agent and decades of usage have clearly established the effectiveness of ICG for human clinical applications. In this study, we have optimized the ICG labelling conditions that is optimal for noninvasive optical imaging and demonstrated that ICG labelled cells can be successfully used for in vivo cell tracking applications in SCID mice injury models.
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Amiri A, Namavari M, Rashidi M, Fahmidehkar MA, Seghatoleslam A. Inhibitory Effects of Cyrtopodion scabrum Extract on Growth of Human Breast and Colorectal Cancer Cells. Asian Pac J Cancer Prev 2015; 16:565-70. [DOI: 10.7314/apjcp.2015.16.2.565] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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The assessment of the in vivo to in vitro cellular transition of human umbilical cord multipotent stromal cells. Placenta 2014; 36:232-9. [PMID: 25524058 DOI: 10.1016/j.placenta.2014.11.024] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2014] [Revised: 11/26/2014] [Accepted: 11/28/2014] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Human umbilical cord stroma is a rich source of primitive multipotent stromal cells (hUC-MSCs). However, the methods for hUC-MSC isolation and propagation remain controversial and vary among laboratories. Our group previously demonstrated that two cell types emerge upon enzymatic isolation of hUC-MSCs, which subsequently undergo a transition towards a fibroblastoid phenotype in later passages. The aim of this study was to further analyse cultured hUC-MSCs by evaluating the cytoskeletal and cell adhesion proteins and by comparing the remodelling of those proteins in umbilical cord sections to determine the cell alterations due to enzymatic and explant methods. METHODS Tissue sections and cultured cells isolated by enzymatic or explant methods were analysed morphologically and by labelling cytokeratin, vimentin, alpha-smooth muscle actin, E-cadherin and N-cadherin profiles. RESULTS The present observations confirmed that wide, flat cells (type-1) share myofibroblastic features, appear exclusively in enzymatically isolated early cultures; gradually diminish or are replaced by fibroblastoid cells (type-2) in later passages. In contrast, the explant method does not result in the existence of type-1 cells in vitro. Among the tested CK subtypes, CK18 expression is upregulated, whereas CK19 expression is downregulated upon culturing after both protocols. Vimentin and α-SMA, as the major intermediate filaments of hUC-MSCs were found unaltered throughout the culturing period regardless of the cell isolation technique used. DISCUSSION The data presented confirm and further elucidate the previously observed phenotypic change in hUC-MSCs as illustrated by alterations in structural proteins during enzymatic isolation and subsequent culturing of cells compared with in situ equivalents.
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Human umbilical cord mesenchymal stem cells infected with adenovirus expressing HGF promote regeneration of damaged neuron cells in a Parkinson's disease model. BIOMED RESEARCH INTERNATIONAL 2014; 2014:909657. [PMID: 25276829 PMCID: PMC4167956 DOI: 10.1155/2014/909657] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2014] [Revised: 07/22/2014] [Accepted: 08/05/2014] [Indexed: 01/22/2023]
Abstract
Parkinson's disease (PD) is a neurodegenerative movement disorder that is characterized by the progressive degeneration of the dopaminergic (DA) pathway. Mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have great potential for developing a therapeutic agent as such. HGF is a multifunctional mediator originally identified in hepatocytes and has recently been reported to possess various neuroprotective properties. This study was designed to investigate the protective effect of hUC-MSCs infected by an adenovirus carrying the HGF gene on the PD cell model induced by MPP+ on human bone marrow neuroblastoma cells. Our results provide evidence that the cultural supernatant from hUC-MSCs expressing HGF could promote regeneration of damaged PD cells at higher efficacy than the supernatant from hUC-MSCs alone. And intracellular free Ca2+ obviously decreased after treatment with cultural supernatant from hUC-MSCs expressing HGF, while the expression of CaBP-D28k, an intracellular calcium binding protein, increased. Therefore our study clearly demonstrated that cultural supernatant of MSC overexpressing HGF was capable of eliciting regeneration of damaged PD model cells. This effect was probably achieved through the regulation of intracellular Ca2+ levels by modulating of CaBP-D28k expression.
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Sabapathy V, Sundaram B, VM S, Mankuzhy P, Kumar S. Human Wharton's Jelly Mesenchymal Stem Cells plasticity augments scar-free skin wound healing with hair growth. PLoS One 2014; 9:e93726. [PMID: 24736473 PMCID: PMC3988008 DOI: 10.1371/journal.pone.0093726] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Accepted: 03/06/2014] [Indexed: 02/07/2023] Open
Abstract
Human mesenchymal stem cells (MSCs) are a promising candidate for cell-based transplantation and regenerative medicine therapies. Thus in the present study Wharton's Jelly Mesenchymal Stem Cells (WJ-MSCs) have been derived from extra embryonic umbilical cord matrix following removal of both arteries and vein. Also, to overcome the clinical limitations posed by fetal bovine serum (FBS) supplementation because of xenogeneic origin of FBS, usual FBS cell culture supplement has been replaced with human platelet lysate (HPL). Apart from general characteristic features of bone marrow-derived MSCs, wharton jelly-derived MSCs have the ability to maintain phenotypic attributes, cell growth kinetics, cell cycle pattern, in vitro multilineage differentiation plasticity, apoptotic pattern, normal karyotype-like intrinsic mesenchymal stem cell properties in long-term in vitro cultures. Moreover, the WJ-MSCs exhibited the in vitro multilineage differentiation capacity by giving rise to differentiated cells of not only mesodermal lineage but also to the cells of ectodermal and endodermal lineage. Also, WJ-MSC did not present any aberrant cell state upon in vivo transplantation in SCID mice and in vitro soft agar assays. The immunomodulatory potential assessed by gene expression levels of immunomodulatory factors upon exposure to inflammatory cytokines in the fetal WJ-MSCs was relatively higher compared to adult bone marrow-derived MSCs. WJ-MSCs seeded on decellularized amniotic membrane scaffold transplantation on the skin injury of SCID mice model demonstrates that combination of WJ-MSCs and decellularized amniotic membrane scaffold exhibited significantly better wound-healing capabilities, having reduced scar formation with hair growth and improved biomechanical properties of regenerated skin compared to WJ-MSCs alone. Further, our experimental data indicate that indocyanin green (ICG) at optimal concentration can be resourcefully used for labeling of stem cells and in vivo tracking by near infrared fluorescence non-invasive live cell imaging of labelled transplanted cells, thus proving its utility for therapeutic applications.
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Affiliation(s)
- Vikram Sabapathy
- Center for Stem Cell Research (CSCR), Christian Medical College (CMC), Bagayam, Vellore, Tamil Nadu, India
| | - Balasubramanian Sundaram
- Center for Stem Cell Research (CSCR), Christian Medical College (CMC), Bagayam, Vellore, Tamil Nadu, India
| | - Sreelakshmi VM
- School of Bioscience and Technology, VIT University, Vellore, Tamil Nadu, India
| | - Pratheesh Mankuzhy
- Center for Stem Cell Research (CSCR), Christian Medical College (CMC), Bagayam, Vellore, Tamil Nadu, India
| | - Sanjay Kumar
- Center for Stem Cell Research (CSCR), Christian Medical College (CMC), Bagayam, Vellore, Tamil Nadu, India
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Sibov TT, Miyaki LAM, Mamani JB, Marti LC, Sardinha LR, Pavon LF, Oliveira DMD, Cardenas WH, Gamarra LF. Evaluation of umbilical cord mesenchymal stem cell labeling with superparamagnetic iron oxide nanoparticles coated with dextran and complexed with Poly-L-lysine. EINSTEIN-SAO PAULO 2013; 10:180-8. [PMID: 23052453 DOI: 10.1590/s1679-45082012000200011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2011] [Accepted: 06/06/2012] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE The objective of this study was to evaluate the effect of the labeling of umbilical cord vein derived mesenchymal stem cells with superparamagnetic iron oxide nanoparticles coated with dextran and complexed to a non-viral transfector agent transfector poly-L-lysine. METHODS The labeling of mesenchymal stem cells was performed using the superparamagnetic iron oxide nanoparticles/dextran complexed and not complexed to poly-L-lysine. Superparamagnetic iron oxide nanoparticles/dextran was incubated with poly-L-lysine in an ultrasonic sonicator at 37°C for 10 minutes for complex formation superparamagnetic iron oxide nanoparticles/dextran/poly-L-lysine by electrostatic interaction. Then, the mesenchymal stem cells were incubated overnight with the complex superparamagnetic iron oxide nanoparticles/dextran/poly-L-lysine and superparamagnetic iron oxide nanoparticles/dextran. After the incubation period the mesenchymal stem cells were evaluated by internalization of the complex superparamagnetic iron oxide nanoparticles/dextran/poly-L-lysine and superparamagnetic iron oxide nanoparticles/dextran by Prussian Blue stain. Cellular viability of labeled mesenchymal stem cells was evaluated by cellular proliferation assay using 5,6-carboxy-fluorescein-succinimidyl ester method and apoptosis detection by Annexin V- Propidium Iodide assay. RESULTS mesenchymal stem cells labeled with superparamagnetic iron oxide nanoparticles/dextran without poly-L-lysine not internalized efficiently the superparamagnetic iron oxide nanoparticles due to its low presence detected within cells. Mesenchymal stem cells labeled with the complex superparamagnetic iron oxide nanoparticles/dextran/poly-L-lysine efficiently internalized the superparamagnetic iron oxide nanoparticles due to greater presence in the cells interior. The viability and apoptosis assays demonstrated that the mesenchymal stem cells labeled and not labeled respectively with the superparamagnetic iron oxide nanoparticles/dextran/poly-L-lysine continue to proliferate over seven days and the percentage of cells in early or late apoptosis is low compared to the percentage of live cells over the three days. CONCLUSION Our results showed that the use of poly-L-lysine complexed with superparamagnetic iron oxide nanoparticles/dextran provides better internalization of these superparamagnetic iron oxide nanoparticles in mesenchymal stem cells Thus, we demonstrated that this type of labeling is not cytotoxic to the mesenchymal stem cells, since the viability and apoptosis assays showed that the cells remain alive and proliferating. The efficiency of this type of labeling in mesenchymal stem cells can provide non-invasive methods for monitoring these cells in vivo.
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Affiliation(s)
- Tatiana Taís Sibov
- Instituto do Cérebro, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
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Miyaki LAM, Sibov TT, Pavon LF, Mamani JB, Gamarra LF. Study of internalization and viability of multimodal nanoparticles for labeling of human umbilical cord mesenchymal stem cells. EINSTEIN-SAO PAULO 2013; 10:189-96. [PMID: 23052454 DOI: 10.1590/s1679-45082012000200012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Accepted: 06/13/2012] [Indexed: 01/29/2023] Open
Abstract
OBJECTIVE To analyze multimodal magnetic nanoparticles-Rhodamine B in culture media for cell labeling, and to establish a study of multimodal magnetic nanoparticles-Rhodamine B detection at labeled cells evaluating they viability at concentrations of 10µg Fe/mL and 100µg Fe/mL. METHODS We performed the analysis of stability of multimodal magnetic nanoparticles-Rhodamine B in different culture media; the mesenchymal stem cells labeling with multimodal magnetic nanoparticles-Rhodamine B; the intracellular detection of multimodal magnetic nanoparticles-Rhodamine B in mesenchymal stem cells, and assessment of the viability of labeled cells by kinetic proliferation. RESULTS The stability analysis showed that multimodal magnetic nanoparticles-Rhodamine B had good stability in cultured Dulbecco's Modified Eagle's-Low Glucose medium and RPMI 1640 medium. The mesenchymal stem cell with multimodal magnetic nanoparticles-Rhodamine B described location of intracellular nanoparticles, which were shown as blue granules co-localized in fluorescent clusters, thus characterizing magnetic and fluorescent properties of multimodal magnetic nanoparticles-Rhodamine B. CONCLUSION The stability of multimodal magnetic nanoparticles-Rhodamine B found in cultured Dulbecco's Modified Eagle's-Low Glucose medium and RPMI 1640 medium assured intracellular mesenchymal stem cells labeling. This cell labeling did not affect viability of labeled mesenchymal stem cells since they continued to proliferate for five days.
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Mesenchymal stem cells for treatment of neurological disorders: a paracrine effect. Tissue Eng Regen Med 2013. [DOI: 10.1007/s13770-013-1087-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Differentiation of hUC-MSC into dopaminergic-like cells after transduction with hepatocyte growth factor. Mol Cell Biochem 2013; 381:183-90. [PMID: 23737134 DOI: 10.1007/s11010-013-1701-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Accepted: 05/24/2013] [Indexed: 02/07/2023]
Abstract
Parkinson's disease (PD) is a common neurodegenerative condition causing significant disability and thus negatively impacting quality of life. The recent advent of stem cell-based therapy has heralded the prospect of a potential restorative treatment option for PD. In particular, mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have great potential for developing a therapeutic agent as such. Furthermore, hepatocyte growth factor (HGF), which shows mitogenic and morphogenetic activities in a variety of cells, including MSC, and may be implicated in the pathophysiology of PD. As such, HGF may represent a new therapeutic target for the disease. In this study, we successfully isolated and facilitated the transduction of an adenoviral vector expressing HGF (Ad-HGF) into isolated hUC-MSCs. Following transduction, the hUC-MSCs can differentiate into dopaminergic neuron-like cells secreting dopamine, tyrosine hydroxylase, and dopamine transporter. Our data suggest that hUC-MSCs have the ability to differentiate into dopaminergic neurons after transduction with Ad-HGF, providing encouraging evidence to further explore this approach to the treatment of PD.
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Inamdar AA, Inamdar AC. Culture conditions for growth of clinical grade human tissue derived mesenchymal stem cells: comparative study between commercial serum-free media and human product supplemented media. ACTA ACUST UNITED AC 2013. [DOI: 10.7243/2050-1218-2-10] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Blumberg SN, Berger A, Hwang L, Pastar I, Warren SM, Chen W. The role of stem cells in the treatment of diabetic foot ulcers. Diabetes Res Clin Pract 2012; 96:1-9. [PMID: 22142631 DOI: 10.1016/j.diabres.2011.10.032] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2011] [Revised: 09/15/2011] [Accepted: 10/24/2011] [Indexed: 12/19/2022]
Abstract
Diabetic foot ulcers (DFUs) are a significant and rapidly growing complication of diabetes and its effects on wound healing. Over half of diabetic patients who develop a single ulcer will subsequently develop another ulcer of which the majority will become chronic non-healing ulcers. One-third will progress to lower extremity amputation. Over the past decade, the outcomes for patients with DFUs ulcers have not improved, despite advances in wound care. Successful treatment of diabetic foot ulcers is hindered by the lack of targeted therapy that hones in on the healing processes dysregulated by diabetes. Stem cells are a promising treatment for DFUs as they are capable of targeting, as well as bypassing, the underlying abnormal healing mechanisms and deranged cell signaling in diabetic wounds and promote healing. This review will focus on existing stem cell technologies and their application in the treatment of DFUs.
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Affiliation(s)
- Sheila N Blumberg
- New York University School of Medicine, Department of Surgery, Division of Wound Healing & Regenerative Medicine, New York, NY 10016, United States
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Arufe MC, Fuente ADL, Fuentes I, Toro FJD, Blanco FJ. Umbilical cord as a mesenchymal stem cell source for treating joint pathologies. World J Orthop 2011; 2:43-50. [PMID: 22474635 PMCID: PMC3302041 DOI: 10.5312/wjo.v2.i6.43] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2011] [Revised: 06/01/2011] [Accepted: 06/08/2011] [Indexed: 02/06/2023] Open
Abstract
Articular cartilage disorders and injuries often result in life-long chronic pain and compromised quality of life. Regrettably, the regeneration of articular cartilage is a continuing challenge for biomedical research. One of the most promising therapeutic approaches is cell-based tissue engineering, which provides a healthy population of cells to the injured site but requires differentiated chondrocytes from an uninjured site. The use of healthy chondrocytes has been found to have limitations. A promising alternative cell population is mesenchymal stem cells (MSCs), known to possess excellent proliferation potential and proven capability for differentiation into chondrocytes. The "immunosuppressive" property of human MSCs makes them an important candidate for allogeneic cell therapy. The use of allogeneic MSCs to repair large defects may prove to be an alternative to current autologous and allogeneic tissue-grafting procedures. An allogeneic cell-based approach would enable MSCs to be isolated from any donor, expanded and cryopreserved in allogeneic MSC banks, providing a readily available source of progenitors for cell replacement therapy. These possibilities have spawned the current exponential growth in stem cell research in pharmaceutical and biotechnology communities. Our objective in this review is to summarize the knowledge about MSCs from umbilical cord stroma and focus mainly on their applications for joint pathologies.
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