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Brembilla NC, El-Harane S, Durual S, Krause KH, Preynat-Seauve O. Adipose-Derived Stromal Cells Exposed to RGD Motifs Enter an Angiogenic Stage Regulating Endothelial Cells. Int J Mol Sci 2025; 26:867. [PMID: 39940638 PMCID: PMC11817220 DOI: 10.3390/ijms26030867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 11/19/2024] [Accepted: 11/26/2024] [Indexed: 02/16/2025] Open
Abstract
Adipose-derived stromal cells (ASCs) possess significant regenerative potential, playing a key role in tissue repair and angiogenesis. During wound healing, ASC interacts with the extracellular matrix by recognizing arginylglycylaspartic acid (RGD) motifs, which are crucial for mediating these functions. This study investigates how RGD exposure influences ASC behavior, with a focus on angiogenesis. To mimic the wound-healing environment, ASC were cultured in a porcine gelatin sponge, an RGD-exposing matrix. Transcriptomics revealed that ASC cultured in gelatin exhibited an upregulated expression of genes associated with inflammation, angiogenesis, and tissue repair compared to ASC in suspension. Pro-inflammatory and pro-angiogenic factors, including IL-1, IL-6, IL-8, and VEGF, were significantly elevated. Functional assays further demonstrated that ASC-conditioned media enhanced endothelial cell migration, tubulogenesis, and reduced endothelial permeability, all critical processes in angiogenesis. Notably, ASC-conditioned media also promoted vasculogenesis in human vascular organoids. The inhibition of ASC-RGD interactions using the cyclic peptide cilengitide reversed these effects, underscoring the essential role of RGD-integrin interactions in ASC-mediated angiogenesis. These findings suggest that gelatin sponges enhance ASC's regenerative and angiogenic properties via RGD-dependent mechanisms, offering promising therapeutic potential for tissue repair and vascular regeneration. Understanding how RGD modulates ASC behavior provides valuable insights into advancing cell-based regenerative therapies.
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Affiliation(s)
| | - Sanae El-Harane
- Department of Medicine, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland;
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland;
| | - Stéphane Durual
- Laboratory of Biomaterials, Faculty of Dental Medicine, University of Geneva, 1206 Geneva, Switzerland;
| | - Karl-Heinz Krause
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland;
| | - Olivier Preynat-Seauve
- Hekestiss Plan-les-Ouates, 1228 Geneva, Switzerland
- Department of Medicine, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland;
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland;
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2
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Farahzadi R, Fathi E, Vandghanooni S, Valipour B. Hydrogel encapsulation of mesenchymal stem cells-derived extracellular vesicles as a novel therapeutic approach in cancer therapy. Biochim Biophys Acta Rev Cancer 2024; 1879:189177. [PMID: 39218403 DOI: 10.1016/j.bbcan.2024.189177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/28/2024] [Accepted: 08/28/2024] [Indexed: 09/04/2024]
Abstract
Cell therapy has emerged as one of the most promising approaches to treating disease in recent decades. The application of stem cells in anti-tumor therapy is determined by their varying capacity for proliferation, migration, and differentiation. These capacities are derived from different sources. The use of stem cell carriers in cancer treatment is justified by the following three reasons: (I) shield therapeutic agents from swift biological deterioration; (II) reduce systemic side effects; and (III) increase local therapeutic levels since stem cells have an innate ability to target tumors. The quantity of stem cells confined to the tumor microenvironment determines this system's anti-tumor activity. Nevertheless, there are limitations to the use of different types of stem cells. When immune cells are used in cell therapy, it may lead to cytokine storms and improper reactions to self-antigens. Furthermore, the use of stem cells may result in cancer. Additionally, after an intravenous injection, cells could not migrate to the injury location. Exosomes derived from different cells were thus proposed as possible therapeutic options. Exosomes are becoming more and more well-liked because of their small size, biocompatibility, and simplicity in storage and separation. A number of investigations have shown that adding various medications and microRNAs to exosomes may enhance their therapeutic effectiveness. Thus, it is essential to evaluate studies looking into the therapeutic effectiveness of encapsulated exosomes. In this review, we looked at studies on encapsulated exosomes' use in regenerative medicine and the treatment of cancer. The results imply that the therapeutic potential increases when encapsulated exosomes are used rather than intact exosomes. Therefore, in order to optimize the effectiveness of the treatment, it is advised to implement this technique in accordance with the kind of therapy.
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Affiliation(s)
- Raheleh Farahzadi
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ezzatollah Fathi
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
| | - Somayeh Vandghanooni
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behnaz Valipour
- Department of Basic Sciences and Health, Sarab Faculty of Medical Sciences, Sarab, East Azerbaijan, Iran.
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3
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Cheng HY, Anggelia MR, Liu SC, Lin CF, Lin CH. Enhancing Immunomodulatory Function of Mesenchymal Stromal Cells by Hydrogel Encapsulation. Cells 2024; 13:210. [PMID: 38334602 PMCID: PMC10854565 DOI: 10.3390/cells13030210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/10/2024] [Accepted: 01/18/2024] [Indexed: 02/10/2024] Open
Abstract
Mesenchymal stromal cells (MSCs) showcase remarkable immunoregulatory capabilities in vitro, positioning them as promising candidates for cellular therapeutics. However, the process of administering MSCs and the dynamic in vivo environment may impact the cell-cell and cell-matrix interactions of MSCs, consequently influencing their survival, engraftment, and their immunomodulatory efficacy. Addressing these concerns, hydrogel encapsulation emerges as a promising solution to enhance the therapeutic effectiveness of MSCs in vivo. Hydrogel, a highly flexible crosslinked hydrophilic polymer with a substantial water content, serves as a versatile platform for MSC encapsulation. Demonstrating improved engraftment and heightened immunomodulatory functions in vivo, MSCs encapsulated by hydrogel are at the forefront of advancing therapeutic outcomes. This review delves into current advancements in the field, with a focus on tuning various hydrogel parameters to elucidate mechanistic insights and elevate functional outcomes. Explored parameters encompass hydrogel composition, involving monomer type, functional modification, and co-encapsulation, along with biomechanical and physical properties like stiffness, viscoelasticity, topology, and porosity. The impact of these parameters on MSC behaviors and immunomodulatory functions is examined. Additionally, we discuss potential future research directions, aiming to kindle sustained interest in the exploration of hydrogel-encapsulated MSCs in the realm of immunomodulation.
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Affiliation(s)
- Hui-Yun Cheng
- Center for Vascularized Composite Allotransplantation, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (M.R.A.)
| | - Madonna Rica Anggelia
- Center for Vascularized Composite Allotransplantation, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (M.R.A.)
- Department of Plastic and Reconstructive Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Shiao-Chin Liu
- Center for Vascularized Composite Allotransplantation, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (M.R.A.)
- Department of Plastic and Reconstructive Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Chih-Fan Lin
- Center for Vascularized Composite Allotransplantation, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (M.R.A.)
| | - Cheng-Hung Lin
- Center for Vascularized Composite Allotransplantation, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (M.R.A.)
- Department of Plastic and Reconstructive Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
- School of Medicine, Chang Gung University, Taoyuan 333, Taiwan
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4
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Liao C, Liu Y, Lin Y, Wang J, Zhou T, Weng W. Mesenchymal Stem Cell-conditioned Medium Protecting Renal Tubular Epithelial Cells by Inhibiting Hypoxia-inducible Factor-1α and Nuclear Receptor Coactivator-1. Curr Stem Cell Res Ther 2024; 19:1369-1381. [PMID: 37817516 DOI: 10.2174/011574888x247652230928064627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 08/09/2023] [Accepted: 08/24/2023] [Indexed: 10/12/2023]
Abstract
BACKGROUND Acute kidney injury (AKI) is characterized by inflammatory infiltration and damage and death of renal tubular epithelial cells (RTECs), in which hypoxia plays an important role. Deferoxamine (DFO) is a well-accepted chemical hypoxia-mimetic agent. Mesenchymal stem cell-conditioned medium (MSC-CM) can reduce local inflammation and repair tissue. In this study, we explored the effect and molecular mechanism of MSC-CM-mediated protection of RTECs under DFO-induced hypoxia. METHODS Rat renal proximal tubule NRK-52E cells were treated with different concentrations of DFO for 24 hours, followed by evaluation of RTEC injury, using a Cell Counting Kit-8 (CCK-8) to detect cell viability and western blotting to evaluate the expression of transforming growth factor- beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), and hypoxia-inducible factor-1 alpha (HIF-1α) in NRK-52E cells. Then, three groups of NRK-52E cells were used in experiments, including normal control (NC), 25 μM DFO, and 25 μM DFO + MSC-CM. MSC-CM was obtained from the human umbilical cord. MSC-CM was used to culture cells for 12 hours before DFO treatment, then fresh MSC-CM and 25 μM DFO were added, and cells were cultured for another 24 hours before analysis. RESULTS Western blotting and cellular immunofluorescence staining showed culture of NRK-52E cells in 25 μM DFO for 24 hours induced HIF-1α and nuclear receptor coactivator-1 (NCoA-1), simulating hypoxia. MSC-CM could inhibit the DFO-induced up-regulation of α-SMA, TGF-β1, HIF-1α and NCoA-1. CONCLUSION Our results suggest that MSC-CM has a protective effect on RTECs by down-regulating HIF-1α and NCoA-1, which may be the harmful factors in renal injury.
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Affiliation(s)
- Chunling Liao
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
| | - Yiping Liu
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
| | - Yongda Lin
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
| | - Jiali Wang
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
| | - Tianbiao Zhou
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
| | - Wenjuan Weng
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
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Syed Mohamed SMD, Welsh GI, Roy I. Renal tissue engineering for regenerative medicine using polymers and hydrogels. Biomater Sci 2023; 11:5706-5726. [PMID: 37401545 DOI: 10.1039/d3bm00255a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/05/2023]
Abstract
Chronic Kidney Disease (CKD) is a growing worldwide problem, leading to end-stage renal disease (ESRD). Current treatments for ESRD include haemodialysis and kidney transplantation, but both are deemed inadequate since haemodialysis does not address all other kidney functions, and there is a shortage of suitable donor organs for transplantation. Research in kidney tissue engineering has been initiated to take a regenerative medicine approach as a potential treatment alternative, either to develop effective cell therapy for reconstruction or engineer a functioning bioartificial kidney. Currently, renal tissue engineering encompasses various materials, mainly polymers and hydrogels, which have been chosen to recreate the sophisticated kidney architecture. It is essential to address the chemical and mechanical aspects of the materials to ensure they can support cell development to restore functionality and feasibility. This paper reviews the types of polymers and hydrogels that have been used in kidney tissue engineering applications, both natural and synthetic, focusing on the processing and formulation used in creating bioactive substrates and how these biomaterials affect the cell biology of the kidney cells used.
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Affiliation(s)
| | - Gavin I Welsh
- Renal Bristol, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS1 3NY, UK
| | - Ipsita Roy
- Department of Materials Science and Engineering, Faculty of Engineering, University of Sheffield, Sheffield S37HQ, UK.
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6
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Mirmoghtadaei M, Khaboushan AS, Mohammadi B, Sadr M, Farmand H, Hassannejad Z, Kajbafzadeh AM. Kidney tissue engineering in preclinical models of renal failure: a systematic review and meta-analysis. Regen Med 2022; 17:941-955. [PMID: 36154467 DOI: 10.2217/rme-2022-0084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: This study aims to compare the efficacy of tissue engineering for kidney reconstruction. Materials & methods: We searched MEDLINE, EMBASE (May 2021), and reference lists of review articles. Results: 19 articles matched our inclusion criteria. A range of natural, synthetic and hybrid scaffolds with or without incorporating cells/growth factors was investigated in 937 animals. More favorable results were observed with a combination of two or more biomaterials, addition of bioactive moieties, and cell seeding. Creatinine concentration, PAX2, collagen type-1, α-SMA, vimentin, IL-1, IL-6 and TNF-α gene expressions were significantly increased compared with native control. Conclusion: Tissue engineering can improve renal function and regeneration; however, further research could benefit from using hybrid scaffolds, stem cells and large animal models.
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Affiliation(s)
- Milad Mirmoghtadaei
- Pediatric Urology & Regenerative Medicine Research Center, Gene, Cell & Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Soltani Khaboushan
- Pediatric Urology & Regenerative Medicine Research Center, Gene, Cell & Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.,Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahareh Mohammadi
- Department of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Matin Sadr
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hooman Farmand
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Hassannejad
- Pediatric Urology & Regenerative Medicine Research Center, Gene, Cell & Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdol-Mohammad Kajbafzadeh
- Pediatric Urology & Regenerative Medicine Research Center, Gene, Cell & Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
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7
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Huang Y, Li X, Yang L. Hydrogel Encapsulation: Taking the Therapy of Mesenchymal Stem Cells and Their Derived Secretome to the Next Level. Front Bioeng Biotechnol 2022; 10:859927. [PMID: 35433656 PMCID: PMC9011103 DOI: 10.3389/fbioe.2022.859927] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 03/03/2022] [Indexed: 01/04/2023] Open
Abstract
Biomaterials have long been the focus of research and hydrogels are representatives thereof. Hydrogels have attracted much attention in the medical sciences, especially as a candidate drug-carrier. Mesenchymal stem cells (MSC) and MSC-derived secretome are a promising therapeutic method, owing to the intrinsic therapeutic properties thereof. The low cell retention and poor survival rate of MSCs make further research difficult, which is a problem that hydrogel encapsulation largely solved. In this review, safety and feasibility of hydrogel-encapsulated MSCs, the improvement of the survival, retention, and targeting, and the enhancement of their therapeutic effect by hydrogels were studied. The status of the hydrogel-encapsulated MSC secretome was also discussed.
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Affiliation(s)
- Yuling Huang
- Departments of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xin Li
- Departments of Infectious Disease, First Affiliated Hospital of China Medical University, Shenyang, China
- *Correspondence: Xin Li, ; Lina Yang,
| | - Lina Yang
- Departments of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang, China
- *Correspondence: Xin Li, ; Lina Yang,
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8
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Zhu R, Yan T, Feng Y, Liu Y, Cao H, Peng G, Yang Y, Xu Z, Liu J, Hou W, Wang X, Li Z, Deng L, Wang S, Li J, Han Q, Li H, Shan G, Cao Y, An X, Yan J, Zhang Z, Li H, Qu X, Zhu J, Zhou S, Wang J, Zhang F, Gao J, Jin R, Xu D, Ma YQ, Huang T, Peng S, Zheng Z, Stambler I, Gilson E, Lim LW, Moskalev A, Cano A, Chakrabarti S, Ulfhake B, Su H, Xu H, Xu S, Wei F, Brown-Borg HM, Min KJ, Ellison-Hughes G, Caruso C, Jin K, Zhao RC. Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms. Cell Res 2021; 31:1244-1262. [PMID: 34702946 PMCID: PMC8546390 DOI: 10.1038/s41422-021-00573-y] [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: 08/14/2021] [Accepted: 09/09/2021] [Indexed: 12/24/2022] Open
Abstract
The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors - CX3CR1 and L-selectin - were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
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Affiliation(s)
- Rongjia Zhu
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Tingdong Yan
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Yingmei Feng
- You'an Hospital, Capital Medical University, Beijing, China
| | - Yan Liu
- Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China
| | - Hongcui Cao
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
- National Clinical Research Center for Infectious Diseases, Hangzhou, Zhejiang, China
| | - Gongxin Peng
- Center for Bioinformatics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Yanlei Yang
- Department of Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhen Xu
- School of Life Sciences, Shanghai University, Shanghai, China
- Versiti Blood Research Institute, Milwaukee, WI, USA
| | - Jingqi Liu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Wei Hou
- You'an Hospital, Capital Medical University, Beijing, China
| | - Xiaoyue Wang
- Center for Bioinformatics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Zhe Li
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Luchan Deng
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Shihua Wang
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Jing Li
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Qin Han
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Hongling Li
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Guangliang Shan
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Yinghao Cao
- Center for Bioinformatics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Xingyan An
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Jianshe Yan
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Zhonghui Zhang
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Huafei Li
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Xuebin Qu
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Jiaqi Zhu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
- National Clinical Research Center for Infectious Diseases, Hangzhou, Zhejiang, China
| | - Shumin Zhou
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Jiao Wang
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Fengchun Zhang
- Department of Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jinming Gao
- Department of Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ronghua Jin
- You'an Hospital, Capital Medical University, Beijing, China.
| | - Dayong Xu
- Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China
| | - Yan-Qing Ma
- Versiti Blood Research Institute, Milwaukee, WI, USA.
| | - Tao Huang
- Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China
| | - Shuang Peng
- Qingdao Walson Standard Biopharmaceutical Co, Ltd, Qingdao, Shangdong, China
| | - Zhi Zheng
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Ilia Stambler
- International Society on Aging and Disease, Bryan, TX, USA
- Department of Science, Technology and Society, Bar Ilan University, Ramat Gan, Israel
| | - Eric Gilson
- International Society on Aging and Disease, Bryan, TX, USA
- Université Côte d'Azur, CNRS, Inserm, IRCAN, Faculty of Medicine, Nice, France
- Department of Medical Genetics, Centre Hospitalier Universitaire (CHU), Nice, France
| | - Lee Wei Lim
- International Society on Aging and Disease, Bryan, TX, USA
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Alexey Moskalev
- International Society on Aging and Disease, Bryan, TX, USA
- Institute of Biology, Komi Science Center of Russian Academy of Sciences, Syktyvkar, Russia
- Russian Gerontological Research Clinical Center, Moscow, Russia
| | - Antonio Cano
- International Society on Aging and Disease, Bryan, TX, USA
- Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Valencia, Spain
| | - Sasanka Chakrabarti
- International Society on Aging and Disease, Bryan, TX, USA
- Maharishi Markandeshwar Deemed University, Mullana-Ambala, India
| | - Brun Ulfhake
- International Society on Aging and Disease, Bryan, TX, USA
- Karolinska University Hospital, Stockholm, Sweden
| | - Huanxing Su
- International Society on Aging and Disease, Bryan, TX, USA
- Institute of Chinese Medical Science, University of Macau, Taipa, Macau, China
| | - Haoying Xu
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Sihuan Xu
- Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China
| | - Feng Wei
- State Key Laboratory of Advanced Materials for Smart Sensing, GRINM GROUP Co, Ltd, Beijing, China
| | - Holly M Brown-Borg
- International Society on Aging and Disease, Bryan, TX, USA
- Department of Biomedical Sciences, University of North Dakota, School of Medicine & Health Sciences, Grand Forks, ND, USA
| | - Kyung-Jin Min
- International Society on Aging and Disease, Bryan, TX, USA
- Department of Biological Sciences, Inha University, Incheon, Republic of Korea
| | - Georgina Ellison-Hughes
- International Society on Aging and Disease, Bryan, TX, USA
- School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
| | - Calogero Caruso
- International Society on Aging and Disease, Bryan, TX, USA
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Kunlin Jin
- International Society on Aging and Disease, Bryan, TX, USA
- University of North Texas Health Science Center, Bryan, TX, USA
| | - Robert Chunhua Zhao
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
- School of Life Sciences, Shanghai University, Shanghai, China.
- International Society on Aging and Disease, Bryan, TX, USA.
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9
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Yang Y, Geng X, Chi K, Liu C, Liu R, Chen X, Hong Q, Cai G. Ultrasound enhances the therapeutic potential of mesenchymal stem cells wrapped in greater omentum for aristolochic acid nephropathy. Stem Cell Res Ther 2021; 12:261. [PMID: 33941258 PMCID: PMC8091698 DOI: 10.1186/s13287-021-02243-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 02/25/2021] [Indexed: 02/07/2023] Open
Abstract
Background Mesenchymal stem cells (MSCs) have been reported to promote regeneration in both subjects with acute kidney injury (AKI) and chronic kidney disease (CKD), but their efficacy remains limited, probably because most of the cells accumulate in the lungs, liver, and spleen after an intravenous infusion. Therefore, ultrasound-guided administration of MSCs represents a possible approach to solve this problem. The greater omentum is used to promote cell survival due to its rich vasculature. We hypothesized that ultrasound-guided administration of MSCs combined with greater omentum might be more curative than currently available approaches. Methods In this study, we established an aristolochic acid nephropathy (AAN) model by intraperitoneally administering aristolochic acid I sodium salt (AA-I) at a dose of 5 mg/kg body weight on alternate days for 4 weeks. Subsequently, a laparotomy was performed, and the left kidney from which the capsule had been removed was wrapped with the greater omentum. A dose of 2 × 107 MSCs was injected into the space between the greater omentum and the left kidney. Equal amounts of MSCs were administered under ultrasound guidance every second week for a total of 4 treatments. Mice were sacrificed 4 weeks after surgery. Serum creatinine and blood urea levels were measured to assess renal function. qPCR, Western blot, and histological analyses were conducted to further investigate the therapeutic mechanism of MSCs. Results Ultrasound-guided injection of MSCs into the greater omentum that surrounds the kidney enriched cells in the kidney region for up to 5 days. Renal function tests indicated that MSCs improved renal function to a great extent, as reflected by decreased blood urea nitrogen and serum creatinine levels. In addition, histological analyses showed that MSCs noticeably attenuated kidney injury, as evidenced by the amelioration of tubular necrosis and peritubular interstitial fibrosis. Mitigation of renal interstitial fibrosis was further confirmed by immunohistochemistry, qPCR, and western blotting after MSC treatment. Moreover, immunofluorescence staining revealed that MSCs alleviated inflammatory responses by increasing the counts of CD206+ cells and decreasing the counts of CD68+ cells. MSC migration was initiated in response to AA-I-treated renal epithelial cells in an in vitro migration assay. Conclusions These findings suggested that administration of MSCs into the cavity formed by the injured kidney and the greater omentum under ultrasound guidance improved renal function, attenuated kidney injury, and mitigated renal interstitial fibrosis and inflammatory responses. Thus, this approach might be a safe and effective therapy for CKD. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02243-7.
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Affiliation(s)
- Yuanjun Yang
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, 100853, China
| | - Xiaodong Geng
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, 100853, China
| | - Kun Chi
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, 100853, China
| | - Chao Liu
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, 100853, China
| | - Ran Liu
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, 100853, China
| | - Xiangmei Chen
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, 100853, China
| | - Quan Hong
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, 100853, China.
| | - Guangyan Cai
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, 100853, China.
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Zhang Z, Li Z, Li Y, Wang Y, Yao M, Zhang K, Chen Z, Yue H, Shi J, Guan F, Ma S. Sodium alginate/collagen hydrogel loaded with human umbilical cord mesenchymal stem cells promotes wound healing and skin remodeling. Cell Tissue Res 2021; 383:809-821. [PMID: 33159581 DOI: 10.1007/s00441-020-03321-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 10/12/2020] [Indexed: 02/03/2023]
Abstract
Stem cell transplantation is a promising therapy for wound healing, but the low retention and survival of transplanted stem cells limit their application. Injectable hydrogels exert beneficial effects in skin tissue engineering. In this study, an injectable hydrogel composed of sodium alginate (SA) and collagen type I (Col) was synthesized as a tissue scaffold to improve the efficacy of stem cells in a full-thickness excision wound model. Our results showed that SA/Col hydrogel was injectable, biodegradable, and exhibited low immunogenicity, which could promote the retention and survival of hUC-MSCs in vivo. SA/Col loaded with hUC-MSCs showed reduced wound size (p < 0.05). Histological and immunofluorescence results confirmed that SA/Col loaded with hUC-MSCs significantly promoted the formation of granulation, enhanced collagen deposition and angiogenesis, increased VEGF and TGF-β1 expression (p < 0.05), and mitigated inflammation evidenced by lower production of TNF-α and IL-1β and higher release of IL-4 and IL-10 (p < 0.05). Furthermore, SA/Col loaded with hUC-MSCs significantly lowered the expression of NLRP3 inflammasome-related proteins (p < 0.05). Taken together, our results suggest that SA/Col loaded with hUC-MSCs promotes skin wound healing via partly inhibiting NLRP3 pathway, which has potential to the treatment of skin wounds.
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Affiliation(s)
- Zhenkun Zhang
- School of Life Sciences, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, 450001, Henan, China
| | - Zhe Li
- School of Life Sciences, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, 450001, Henan, China
| | - Ya Li
- School of Life Sciences, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, 450001, Henan, China
| | - Yingying Wang
- School of Life Sciences, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, 450001, Henan, China
| | - Minghao Yao
- School of Life Sciences, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, 450001, Henan, China
| | - Kun Zhang
- School of Life Sciences, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, 450001, Henan, China
| | - Zhenyu Chen
- School of Life Sciences, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, 450001, Henan, China
| | - Han Yue
- Stem Cell Research Center, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, China
| | - Jijing Shi
- Central Lab of the First People's Hospital of Zhengzhou, Zhengzhou, 450001, Henan, China
| | - Fangxia Guan
- School of Life Sciences, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, 450001, Henan, China
- Stem Cell Research Center, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, China
| | - Shanshan Ma
- School of Life Sciences, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, 450001, Henan, China.
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Burdeyron P, Giraud S, Hauet T, Steichen C. Urine-derived stem/progenitor cells: A focus on their characterization and potential. World J Stem Cells 2020; 12:1080-1096. [PMID: 33178393 PMCID: PMC7596444 DOI: 10.4252/wjsc.v12.i10.1080] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 06/26/2020] [Accepted: 08/24/2020] [Indexed: 02/06/2023] Open
Abstract
Cell therapy, i.e., the use of cells to repair an affected tissue or organ, is at the forefront of regenerative and personalized medicine. Among the multiple cell types that have been used for this purpose [including adult stem cells such as mesenchymal stem cells or pluripotent stem cells], urine-derived stem cells (USCs) have aroused interest in the past years. USCs display classical features of mesenchymal stem cells such as differentiation capacity and immunomodulation. Importantly, they have the main advantage of being isolable from one sample of voided urine with a cheap and unpainful procedure, which is broadly applicable, whereas most adult stem cell types require invasive procedure. Moreover, USCs can be differentiated into renal cell types. This is of high interest for renal cell therapy-based regenerative approaches. This review will firstly describe the isolation and characterization of USCs. We will specifically present USC phenotype, which is not an object of consensus in the literature, as well as detail their differentiation capacity. In the second part of this review, we will present and discuss the main applications of USCs. These include use as a substrate to generate human induced pluripotent stem cells, but we will deeply focus on the use of USCs for cell therapy approaches with a detailed analysis depending on the targeted organ or system. Importantly, we will also focus on the applications that rely on the use of USC-derived products such as microvesicles including exosomes, which is a strategy being increasingly employed. In the last section, we will discuss the remaining barriers and challenges in the field of USC-based regenerative medicine.
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Affiliation(s)
- Perrine Burdeyron
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers 86021, France
| | - Sébastien Giraud
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Service de Biochimie, CHU de Poitiers, Poitiers 86021, France
| | - Thierry Hauet
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers 86021, France
- Service de Biochimie, CHU de Poitiers, Poitiers 86021, France
| | - Clara Steichen
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers 86021, France.
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