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Del Prete C, Attolini E, Merlo B, Iacono E, Nocera FP, De Martino L, Longobardi C, Damiano S, Longobardi V, Cocchia N, Pasolini MP. Post-Insemination Infusion of Wharton's Jelly Mesenchymal Stromal/Stem Cells-Derived Conditioned Medium: A Novel Approach for Improving Pregnancy Outcomes in Problem Mares. Vet Sci 2025; 12:482. [PMID: 40431575 PMCID: PMC12115377 DOI: 10.3390/vetsci12050482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 05/07/2025] [Accepted: 05/14/2025] [Indexed: 05/29/2025] Open
Abstract
Treating endometritis is one of the major challenges faced by veterinarians. The effect of post-insemination intrauterine infusion Wharton's jelly mesenchymal stromal/stem cell-derived conditioned medium (WJ-MSC-CM) on the uterine response and pregnancy outcomes in problem mares was evaluated in this study. The cycles of 12 problem mares were treated seven/eight hours after insemination with intrauterine infusion of 20 mL of WJ-MSC-CM (TRT) or non-conditioned Ringer's lactate solution (CTR). Before (PRE) and 12 h after (POST) treatment, an ultrasonographic examination and a low-volume flush (LVF) for efflux clarity evaluation and bacteriological and cytological analysis were made. Pregnancy diagnosis was performed at 14 days and confirmed at 60 days after ovulation. A decrease (p < 0.05) in polymorphonuclear neutrophils infiltration and a trend toward significance in LVF efflux clarity (p < 0.1) were observed in TRT cycles. The TRT (50%) had a higher pregnancy rate (p < 0.05) than CTR group (0%) at first cycle. Only a trend toward significance was observed comparing pregnancy frequencies between the two groups (CTR 12.5% vs. TRT 54.5%), the pregnancy rate of TRT cycles was comparable to that of normal mares (p > 0.05) and higher (p < 0.05) than that reported for problem mares in the literature. Post-insemination uterine infusion of WJ-MSC-CM in mares restores pregnancy rates to normal levels, by its anti-inflammatory effect.
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Affiliation(s)
- Chiara Del Prete
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy; (C.D.P.); (F.P.N.); (L.D.M.); (C.L.); (S.D.); (V.L.); (N.C.); (M.P.P.)
| | - Emilia Attolini
- Department of Veterinary Medical Sciences, Alma Mater Studiorum-University of Bologna, 40064 Ozzano dell’Emilia, Italy; (E.A.); (E.I.)
| | - Barbara Merlo
- Department of Veterinary Medical Sciences, Alma Mater Studiorum-University of Bologna, 40064 Ozzano dell’Emilia, Italy; (E.A.); (E.I.)
| | - Eleonora Iacono
- Department of Veterinary Medical Sciences, Alma Mater Studiorum-University of Bologna, 40064 Ozzano dell’Emilia, Italy; (E.A.); (E.I.)
| | - Francesca Paola Nocera
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy; (C.D.P.); (F.P.N.); (L.D.M.); (C.L.); (S.D.); (V.L.); (N.C.); (M.P.P.)
| | - Luisa De Martino
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy; (C.D.P.); (F.P.N.); (L.D.M.); (C.L.); (S.D.); (V.L.); (N.C.); (M.P.P.)
| | - Consiglia Longobardi
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy; (C.D.P.); (F.P.N.); (L.D.M.); (C.L.); (S.D.); (V.L.); (N.C.); (M.P.P.)
| | - Sara Damiano
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy; (C.D.P.); (F.P.N.); (L.D.M.); (C.L.); (S.D.); (V.L.); (N.C.); (M.P.P.)
| | - Valentina Longobardi
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy; (C.D.P.); (F.P.N.); (L.D.M.); (C.L.); (S.D.); (V.L.); (N.C.); (M.P.P.)
| | - Natascia Cocchia
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy; (C.D.P.); (F.P.N.); (L.D.M.); (C.L.); (S.D.); (V.L.); (N.C.); (M.P.P.)
| | - Maria Pia Pasolini
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy; (C.D.P.); (F.P.N.); (L.D.M.); (C.L.); (S.D.); (V.L.); (N.C.); (M.P.P.)
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Ali A, Kuo WW, Kuo CH, Lo JF, Hsieh DJY, Pai P, Ho TJ, Shibu MA, Lin SZ, Huang CY. Chaperone-assisted E3 ligase-engineered mesenchymal stem cells target hyperglycemia-induced p53 for ubiquitination and proteasomal degradation ameliorates self-renewal. Biol Res 2025; 58:20. [PMID: 40270049 PMCID: PMC12020092 DOI: 10.1186/s40659-025-00604-7] [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: 01/18/2025] [Accepted: 04/09/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND Stem cell therapies may potentially be used in regenerative and reconstructive medicine due to their ability for self-renewal and differentiation. Stressful conditions, such as hyperglycemia, adversely affect stem cell functions, impairing their function and promoting differentiation by opposing self-renewal. The carboxyl terminus of HSP70 interacting protein (CHIP), which is a cochaperone and E3 ligase, maintains protein homeostasis and performs quality control of the cell via ubiquitylation. However, the role of CHIP in regulating stemness remains unknown. RESULTS Hyperglycemia downregulated CHIP-induced p53, arrested the cell cycle at the gap (G1) phase, and promoted the loss of stemness in WJMSCs. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, immunofluorescence, and cell cycle analysis showed that CHIP-overexpressing WJMSCs downregulated the expression of phosphorylated p53 and shortened its half-life while enhancing self-renewal factors. Additionally, co-IP and Western blotting revealed that CHIP promoted the ubiquitination and proteasomal degradation of hyperglycemia-induced p53 through the chaperone system. CONCLUSIONS CHIP may promote ubiquitin-mediated proteasomal degradation of hyperglycemia-induced p53 rescues self-renewal genes, which can maintain the long-term undifferentiated state of WJMSCs. CHIP may be an alternative therapeutic option in regenerative medicine for hyperglycemic-related complications in diabetes.
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Affiliation(s)
- Ayaz Ali
- Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK
- Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan
| | - Wei-Wen Kuo
- Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan
| | - Chia-Hua Kuo
- Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan
| | - Jeng-Feng Lo
- Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan
| | | | - Peiying Pai
- School of Medicine, College of Medicine, China Medical University, Taichung, 40402, Taiwan
- Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, 40447, Taiwan
| | - Tsung-Jung Ho
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
| | | | - Shinn-Zong Lin
- Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan
- Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan
| | - Chih-Yang Huang
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 404, Taiwan.
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
- Department of Biotechnology, Asia University, Taichung, Taiwan.
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan.
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Taghdi MH, Al-Masawa ME, Muttiah B, Fauzi MB, Law JX, Zainuddin AA, Lokanathan Y. Three-Dimensional Bioprinted Gelatin-Genipin Hydrogels Enriched with hUCMSC-Derived Small Extracellular Vesicles for Regenerative Wound Dressings. Polymers (Basel) 2025; 17:1163. [PMID: 40362948 PMCID: PMC12073717 DOI: 10.3390/polym17091163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2025] [Revised: 04/17/2025] [Accepted: 04/21/2025] [Indexed: 05/15/2025] Open
Abstract
Mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) have shown great promise in promoting tissue repair, including skin wound healing, but challenges like rapid degradation and short retention have limited their clinical application. Hydrogels have emerged as effective carriers for sustained EV release. Three-dimensional printing enables the development of personalized skin substitutes tailored to the wound size and shape. This study aimed to develop 3D bioprinted gelatin-genipin hydrogels incorporating human umbilical cord MSC-sEVs (hUCMSC-sEVs) for future skin wound healing applications. Gelatin hydrogels (8% and 10% w/v) were crosslinked with 0.3% genipin (GECL) to improve stability. The hydrogels were evaluated for their suitability for extrusion-based 3D bioprinting and physicochemical properties, such as the swelling ratio, hydrophilicity, enzymatic degradation, and water vapor transmission rate (WVTR). Chemical characterization was performed using EDX, XRD, and FTIR. The hUCMSC-sEVs were isolated via centrifugation and tangential flow filtration (TFF) and characterized. The crosslinked hydrogels were successfully 3D bioprinted and demonstrated superior properties, including high hydrophilicity, a swelling ratio of ~500%, slower degradation, and optimal WVTR. hUCMSC-sEVs, ranging from 50 to 200 nm, were positive for surface and cytosolic markers. Adding 75 μg/mL of hUCMSC-EVs into 10% GECL hydrogels significantly improved the biocompatibility. These hydrogels offer ideal properties for 3D bioprinting and wound healing, demonstrating their potential as biomaterial scaffolds for skin tissue regeneration applications.
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Affiliation(s)
- Manal Hussein Taghdi
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; (M.H.T.); (M.E.A.-M.); (B.M.); (M.B.F.); (J.X.L.)
- Department of Anesthesia and Intensive Care, Faculty of Medical Technology, University of Tripoli, Tripoli P.O. Box 13932, Libya
| | - Maimonah Eissa Al-Masawa
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; (M.H.T.); (M.E.A.-M.); (B.M.); (M.B.F.); (J.X.L.)
| | - Barathan Muttiah
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; (M.H.T.); (M.E.A.-M.); (B.M.); (M.B.F.); (J.X.L.)
| | - Mh Busra Fauzi
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; (M.H.T.); (M.E.A.-M.); (B.M.); (M.B.F.); (J.X.L.)
- Advance Bioactive Materials-Cells UKM Research Group, Universiti Kebangsaan Malaysia, Bangi 43600, Malaysia
| | - Jia Xian Law
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; (M.H.T.); (M.E.A.-M.); (B.M.); (M.B.F.); (J.X.L.)
| | - Ani Amelia Zainuddin
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia;
| | - Yogeswaran Lokanathan
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; (M.H.T.); (M.E.A.-M.); (B.M.); (M.B.F.); (J.X.L.)
- Advance Bioactive Materials-Cells UKM Research Group, Universiti Kebangsaan Malaysia, Bangi 43600, Malaysia
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Yueh PF, Chiang IT, Weng YS, Liu YC, Wong RCB, Chen CY, Hsu JBK, Jeng LB, Shyu WC, Hsu FT. Innovative dual-gene delivery platform using miR-124 and PD-1 via umbilical cord mesenchymal stem cells and exosome for glioblastoma therapy. J Exp Clin Cancer Res 2025; 44:107. [PMID: 40134003 PMCID: PMC11934454 DOI: 10.1186/s13046-025-03336-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 02/18/2025] [Indexed: 03/27/2025] Open
Abstract
Addressing the challenges of identifying suitable targets and effective delivery strategies is critical in pursuing therapeutic solutions for glioblastoma (GBM). This study focuses on the therapeutic potential of microRNA-124 (miR-124), known for its tumor-suppressing properties, by investigating its ability to target key oncogenic pathways in GBM. The results reveal that CDK4 and CDK6-cyclin-dependent kinases that promote cell cycle progression-are significantly overexpressed in GBM brain samples, underscoring their role in tumor proliferation and identifying them as critical targets for miR-124 intervention. However, delivering miRNA-based therapies remains a major obstacle due to the instability of RNA molecules and the difficulty in achieving targeted, efficient delivery. To address these issues, this research introduces an innovative, non-viral dual-gene delivery platform that utilizes umbilical cord mesenchymal stem cells (UMSCs) and their exosomes to transport miR-124 and programmed cell death protein-1 (PD-1). The efficacy of this dual-gene delivery system was validated using an orthotopic GBM model, which closely mimics the tumor microenvironment seen in patients. Experimental results demonstrate that the UMSC/miR-124-PD-1 complex and its exosomes successfully induce apoptosis in GBM cells, significantly inhibiting tumor growth. Notably, these treatments show minimal cytotoxic effects on normal glial cells, highlighting their safety and selectivity. Moreover, the study highlights the immunomodulatory properties of UMSC/miR-124-PD-1 and its exosomes, enhancing the activation of immune cells such as T cells and dendritic cells, while reducing immunosuppressive cells populations like regulatory T cells and myeloid-derived suppressor cells. The orchestrated dual-gene delivery system by UMSCs and exosomes showcased targeted tumor inhibition and positive immune modulation, emphasizing its potential as a promising therapeutic approach for GBM.
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Affiliation(s)
- Po-Fu Yueh
- Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, 112, Taipei, Beitou, Taiwan (ROC)
| | - I-Tsang Chiang
- Research assistant Center, Show Chwan Memorial Hospital, 500, Changhua, Taiwan (ROC)
- Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, 406, Taichung, Taiwan (ROC)
- Department of Radiation Oncology, Show Chwan Memorial Hospital, Changhua, Taiwan (ROC)
| | - Yueh-Shan Weng
- Department of Biological Science and Technology, China Medical University, 406, Taichung, Taiwan (ROC)
| | - Yu-Chang Liu
- Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, 406, Taichung, Taiwan (ROC)
- Department of Radiation Oncology, Chang Bing Show Chwan Memorial Hospital, 505, Lukang, Changhua, Taiwan (ROC)
- LOHAS Naturopathic Medical Center, Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (ROC)
- Evidence-Based Medicine Center, Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (ROC)
- Center of Quality Management, Chang Bing Show Chwan Memorial Hospital, Lukang, Taiwan (ROC)
| | - Raymond C B Wong
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, 3002, East Melbourne, VIC, Australia
- Ophthalmology, Department of Surgery, University of Melbourne, 3002, East Melbourne, VIC, Australia
| | - Cheng-Yu Chen
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taipei, Taiwan (ROC)
- Department of Medical Imaging, Taipei Medical University Hospital, 112, Taipei, Taiwan (ROC)
| | - Justin Bo-Kai Hsu
- Department of Computer Science and Engineering, Yuan Ze University, 320, Taoyuan, Taiwan (ROC)
| | - Long-Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, 404, Taichung, Taiwan (ROC).
- Cell Therapy Center, China Medical University Hospital, 404, Taichung, Taiwan (ROC).
- School of Medicine, China Medical University, 404, Taichung, Taiwan (ROC).
| | - Woei-Cherng Shyu
- Graduate Institute of Biomedical Sciences, China Medical University, 404, Taichung, Taiwan (ROC).
- Neuroscience and Brain Disease Center, China Medical University, 404, Taichung, Taiwan (ROC).
- Translational Medicine Research Center, Drug Development Center, Department of Neurology, China Medical University & Hospital, 404, Taichung, Taiwan (ROC).
| | - Fei-Ting Hsu
- Department of Biological Science and Technology, China Medical University, 406, Taichung, Taiwan (ROC).
- Department of Life Sciences, National Central University, 320, Taoyuan, Taiwan (ROC).
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Afshari A, Azarpira N, Pakbaz S. Differentiation of Wharton's jelly-derived mesenchymal stromal cells into hepatocyte-like cells using a refined method. BMC Mol Cell Biol 2025; 26:9. [PMID: 40033232 PMCID: PMC11874389 DOI: 10.1186/s12860-025-00534-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Accepted: 02/24/2025] [Indexed: 03/05/2025] Open
Abstract
BACKGROUND The production of functional hepatocyte cells in enough quantities is of paramount importance for the replacement of lost hepatocytes. In this investigation, a series of 7-mimic microRNAs was harnessed to induce the differentiation of Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs) into hepatocyte-like cells (HLC) through the application of two distinct techniques: transfection agents and electroporation. The results were then compared with those of HLCs differentiated through the consumption of chemical compounds. RESULTS Different time points (48 h, 72 h, and 96 h), unlike concentrations of mimic miRNAs (100 pM, and 200 pM), and dissimilar combinations of mimic-miRNAs (4-mimic and 7-mimic miRNAs) were selected to assess the stage of differentiated cells through electroporation and lipofection methods. For chemical differentiation, a two-step chemical hepatic differentiation protocol was used (for 21 days). The expression level of eleven key genes that were selected to estimate the stage of produced HLCs by each method were tested at different time points, concentrations and combination of mimic-miRNA. Results demonstrated that the 7-miR-mimics/72 h culture method by electroporation, then the 7-miR-mimics/72 h culture method by lipofection, and finally the chemical differentiation (72 h culture) showed the best result for differentiation. Furthermore, the period in which HLCs are maintained under culture conditions is important, as prolonged culture (more than 72 h) leads to cell loss. CONCLUSION In conclusion, the results demonstrated that the 7-miR cocktail delivered by electroporation after 72 h effectively promoted the acquisition of hepatocyte-like characteristics which was evidenced by a significant decrease in the Oct4 stemness factor and an increase in the expression of ALB, TAT, AAT, CYP, G6P and HNF4A.
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Affiliation(s)
- Afsoon Afshari
- Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, 7193711351, Iran.
| | - Sara Pakbaz
- Department of Pathology and Laboratory Medicine, University of Toronto, Toronto, Canada
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Xiong M, Kong C, Lu Y, Liu J, Ding W, Zhang T, Zuo W, Cao L, Lu Q, Li A, Li C, Ding L, Yan Y, Ke B, Wan C. Construction of tetravalent bispecific Tandab (CD3/BCMA)-secreting human umbilical cord mesenchymal stem cells and its efficiency in the treatment of multiple myeloma. Stem Cell Res Ther 2025; 16:69. [PMID: 39939863 PMCID: PMC11823243 DOI: 10.1186/s13287-025-04212-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 01/30/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Highly efficient targeted therapy is urgently needed for multiple myeloma (MM). Mesenchymal stem cells (MSCs) are an attractive candidate of cell-based, targeted therapy due to their inherent tumor tropism. However, there is still no MSCs-based tandem diabody for treating MM. METHODS Here, we designed a dual-target therapeutic system in which human umbilical cord MSCs (UCMSCs) were engineered to produce and deliver Tandab (CD3/BCMA), a tetravalent bispecific tandem diabody with two binding sites for CD3 and two for B-cell maturation antigen (BCMA). Western blot and flow cytometry were used to confirm the lentivirus-mediated construction of UCMSCs for diabody expression. The tropism of MSCs towards H929 cells in vitro was determined by migration assays, and the in vivo homing capacity of MSCs was analyzed by immunofluorescence staining. The activation and antitumor efficacy of human T cells mediated by MSCs secreting Tandab (CD3/BCMA) were evaluated in vitro. Finally, an MM xenograft NOD/SCID mouse model was established to investigate the therapeutic effect in vivo. RESULTS We successfully constructed MSCs that can continuously secrete bioactive Tandab (CD3/BCMA), whereby lentiviral transduction did not affect the morphology, proliferation, and lineage differentiation potential of the MSCs. The tropism of MSC-Tandab for MM was verified both in vitro and in vivo. Furthermore, MSC-Tandab promoted the expansion and activation of primary human T cells and induced healthy donor T cells to selectively eliminate BCMA-positive cell lines and primary blasts from patients but not BCMA-negative cells. A similar ability was also observed in the patient-derived T cells. Finally, MSC-Tandab significantly alleviated the MM xenograft tumor burden in NOD/SCID mice without toxic side effects in vivo, whereby the cytokine levels (IFN-γ) in the peripheral blood (PB) were higher in the MSC-Tandab group, and the tumor infiltration of T cells was significantly enhanced. CONCLUSIONS These results suggest that UCMSCs releasing Tandab (CD3/BCMA) are a promising new tool for the treatment of MM, opening a new avenue for the development of cell-based therapy.
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Affiliation(s)
- Mengshang Xiong
- Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China
- Jiangxi Province Key Laboratory of Hematologic Diseases, Nanchang, 330006, China
| | - Chunfang Kong
- Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China
- Jiangxi Province Key Laboratory of Hematologic Diseases, Nanchang, 330006, China
| | - Yang Lu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China
- Tianjin Institutes of Health Science, Tianjin, 301600, China
| | - Jiaojun Liu
- Obstetrics and Gynecology Department, Shanggao County People's Hospital, Yichun, 331100, Jiangxi, China
| | - Weirong Ding
- Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China
- Jiangxi Province Key Laboratory of Hematologic Diseases, Nanchang, 330006, China
| | - Tingting Zhang
- Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China
- Jiangxi Province Key Laboratory of Hematologic Diseases, Nanchang, 330006, China
| | - Wei Zuo
- Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China
- Jiangxi Province Key Laboratory of Hematologic Diseases, Nanchang, 330006, China
| | - Lixia Cao
- Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China
- Jiangxi Province Key Laboratory of Hematologic Diseases, Nanchang, 330006, China
| | - Qiling Lu
- Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China
- Jiangxi Province Key Laboratory of Hematologic Diseases, Nanchang, 330006, China
| | - Anna Li
- Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China
- Jiangxi Province Key Laboratory of Hematologic Diseases, Nanchang, 330006, China
| | - Chaoyu Li
- Jiangxi Medical College, Nanchang University, Nanchang, 330006, China
- Institute of Clinical Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China
| | - Liting Ding
- Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial People's Hospital, Nanchang, 330001, China
| | - Yutao Yan
- Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial People's Hospital, Nanchang, 330001, China
| | - Bo Ke
- Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China.
- Jiangxi Province Key Laboratory of Hematologic Diseases, Nanchang, 330006, China.
- Medical College of Nanchang University, Nanchang, 330006, Jiangxi, China.
| | - Caishui Wan
- Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China.
- Jiangxi Province Key Laboratory of Hematologic Diseases, Nanchang, 330006, China.
- Medical College of Nanchang University, Nanchang, 330006, Jiangxi, China.
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Yarahmadi A, Dorri Giv M, Hosseininejad R, Rezaie A, Mohammadi N, Afkhami H, Farokhi A. Mesenchymal stem cells and their extracellular vesicle therapy for neurological disorders: traumatic brain injury and beyond. Front Neurol 2025; 16:1472679. [PMID: 39974358 PMCID: PMC11835705 DOI: 10.3389/fneur.2025.1472679] [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: 07/29/2024] [Accepted: 01/08/2025] [Indexed: 02/21/2025] Open
Abstract
Traumatic brain injury (TBI) is a complex condition involving mechanisms that lead to brain dysfunction and nerve damage, resulting in significant morbidity and mortality globally. Affecting ~50 million people annually, TBI's impact includes a high death rate, exceeding that of heart disease and cancer. Complications arising from TBI encompass concussion, cerebral hemorrhage, tumors, encephalitis, delayed apoptosis, and necrosis. Current treatment methods, such as pharmacotherapy with dihydropyridines, high-pressure oxygen therapy, behavioral therapy, and non-invasive brain stimulation, have shown limited efficacy. A comprehensive understanding of vascular components is essential for developing new treatments to improve blood vessel-related brain damage. Recently, mesenchymal stem cells (MSCs) have shown promising results in repairing and mitigating brain damage. Studies indicate that MSCs can promote neurogenesis and angiogenesis through various mechanisms, including releasing bioactive molecules and extracellular vesicles (EVs), which help reduce neuroinflammation. In research, the distinctive characteristics of MSCs have positioned them as highly desirable cell sources. Extensive investigations have been conducted on the regulatory properties of MSCs and their manipulation, tagging, and transportation techniques for brain-related applications. This review explores the progress and prospects of MSC therapy in TBI, focusing on mechanisms of action, therapeutic benefits, and the challenges and potential limitations of using MSCs in treating neurological disorders.
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Affiliation(s)
- Aref Yarahmadi
- Department of Biology, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran
| | - Masoumeh Dorri Giv
- Nuclear Medicine Research Center, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Hosseininejad
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Azin Rezaie
- Department of Microbiology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Narges Mohammadi
- Department of Molecular Cell Biology and Microbiology, Faculty of Biological Sciences and Technologies, University of Isfahan, Isfahan, Iran
| | - Hamed Afkhami
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran
| | - Arastoo Farokhi
- Department of Anesthesiology, Kermanshah University of Medical Sciences, Imam Reza Hospital, Kermanshah, Iran
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8
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Khazaeel K, Sadeghi A, Khademi Moghaddam F, Mohammadi T. The impact of graphene quantum dots on osteogenesis potential of Wharton's jelly mesenchymal stem cells in fibrin hydrogel scaffolds. Cytotechnology 2025; 77:14. [PMID: 39665046 PMCID: PMC11628478 DOI: 10.1007/s10616-024-00672-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 11/26/2024] [Indexed: 12/13/2024] Open
Abstract
Bone tissue engineering is a promising approach to overcome the limitations of traditional autograft bone transplantation. Graphene quantum dots (GQDs) have been suggested as an enhancement for osteogenic differentiation. This study aimed to investigate the ability of the fibrin hydrogel scaffold in the presence of graphene quantum dots to promote osteogenic differentiation of human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs). The hWJ-MSCs were isolated from the Wharton's jelly of the human umbilical cord using a mechanical method. Fibrin hydrogel scaffolds were prepared by mixing 15 µl of thrombin solution with fibrinogen solution. GQDs were incorporated into the scaffolds at concentrations of 0, 5, and 10 µg/ml. Cell viability was determined through DAPI staining and the MTT assay. Osteogenic differentiation was assessed by measuring alkaline phosphatase (ALP) activity, quantifying calcium deposition using Alizarin Red S staining, and analyzing the gene expression of BGLAP, COL1A1, Runx-2 and ALP via qPCR. Scanning electron microscopy (SEM) was employed to analyze the scaffold architecture. SEM analysis revealed that the fibrin hydrogel exhibited a suitable architecture for tissue engineering, and DAPI staining confirmed cell viability. The MTT results indicated that the GQDs and fibrin hydrogel scaffold exhibited no cytotoxic effects. Furthermore, the incorporation of GQDs at a concentration of 10 µg/ml significantly enhanced ALP activity, calcium deposition, and the expression of osteogenesis-related genes compared to the control. The findings suggest that the combination of fibrin hydrogel and GQDs can effectively promote the osteogenic differentiation of hWJ-MSCs, contributing to the advancement of bone tissue engineering.
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Affiliation(s)
- Kaveh Khazaeel
- Department of Basic Sciences, Division of Anatomy and Embryology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
- Stem Cells and Transgenic Technology Research Center (STTRC), Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Abbas Sadeghi
- Department of Basic Sciences, Division of Anatomy and Embryology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | | | - Tayebeh Mohammadi
- Department of Basic Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran
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9
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Ghamrawi A, Basso R, Shakik N, Haddad L, Nasr Z, Harmouch C. Wharton's Jelly Mesenchymal Stem Cells: Shaping the Future of Osteoarthritis Therapy with Advancements in Chitosan-Hyaluronic Acid Scaffolds. Stem Cells Dev 2025; 34:1-16. [PMID: 39605205 DOI: 10.1089/scd.2024.0033] [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] [Indexed: 11/29/2024] Open
Abstract
This review explores the potential of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) in cartilage regeneration and osteoarthritis treatment. It covers key factors influencing chondrogenesis, including growth factors, cytokines, and hypoxia, focusing on precise timing. The effectiveness of three-dimensional cultures and scaffold-based strategies in chondrogenic differentiation is discussed. Specific biomaterials such as chitosan and hyaluronic acid are highlighted for tissue engineering. The document reviews clinical applications, incorporating evidence from animal research and early trials and molecular and histological assessments of chondrogenic differentiation processes. It addresses challenges and strategies for optimizing MSC-derived chondrocyte therapy, emphasizing the immunomodulatory properties of these cells. The review concludes as a comprehensive road map for future research and clinical applications in regenerative medicine.
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Affiliation(s)
- Ahed Ghamrawi
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon
| | - Rasha Basso
- Department of Medical Laboratory Sciences, Faculty of Health Sciences University of Balamand, Beirut, Lebanon
| | - Nour Shakik
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon
| | - Lara Haddad
- Department of Medical Laboratory Sciences, Faculty of Health Sciences University of Balamand, Beirut, Lebanon
| | - Zeina Nasr
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon
| | - Chaza Harmouch
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon
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10
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Cheng JH, Chen CW, Chou WY, Chen PC, Wu KT, Jhan SW, Hsu SL, Wu YN, Chen HT. Comparative Analysis of Extracorporeal Shockwave Therapy, Bisphosphonate, and Wharton Jelly-Derived Mesenchymal Stem Cells in Preserving Bone and Cartilage Integrity and Modulating IL31, IL33, and BMP2 in the Cartilage of Ovariectomized Rat Model. Biomedicines 2024; 12:2823. [PMID: 39767728 PMCID: PMC11673226 DOI: 10.3390/biomedicines12122823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 12/09/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Osteoporosis (OP) is a chronic inflammatory bone disease characterized by reduced bone structure and strength, leading to increased fracture risk. Effective therapies targeting both bone and cartilage are limited. This study compared the therapeutic effects of extracorporeal shockwave therapy (ESWT), bisphosphonate (Aclasta), and human Wharton jelly-derived mesenchymal stem cells (WJMSCs) in a rat model of OP. Methods: Female rats were assigned to four groups: Sham (no surgery or treatment), OP (bilateral ovariectomy, OVX), ESWT (OVX + ESWT on both tibias at 0.25 mJ/mm2, 1500 impulses per tibia), Aclasta (OVX + zoledronic acid 0.1 mg/kg via tail vein injection), and WJMSC (OVX + 2 × 10⁶ WJMSCs). Pathological changes, bone microarchitecture (by micro-CT), serum cytokines (by ELISA), and tissue-specific molecular markers (by immunohistochemistry) were evaluated. Results: All treatments improved bone density, preserved cartilage, and modulated cytokines (IL31, IL33, VEGF, and BMP2), with Aclasta showing the greatest improvements in bone parameters and cartilage preservation. ESWT and WJMSC also demonstrated significant effects, with ESWT highlighting non-invasive chondroprotective potential. Conclusions: Aclasta provided the best overall therapeutic response, particularly in bone regeneration. However, ESWT and WJMSC also showed comparable chondroprotective effects. ESWT emerges as a promising non-invasive alternative for OP management when pharmacological or cell-based therapies are not feasible.
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Affiliation(s)
- Jai-Hong Cheng
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (J.-H.C.); (W.-Y.C.); (K.-T.W.); (S.-W.J.); (S.-L.H.)
- Medical Research, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Cheng-Wei Chen
- Department of Orthopedic Surgery, Sports Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
| | - Wen-Yi Chou
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (J.-H.C.); (W.-Y.C.); (K.-T.W.); (S.-W.J.); (S.-L.H.)
- Department of Orthopedic Surgery, Sports Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
| | - Po-Cheng Chen
- Department of Physical Medicine and Rehabilitation, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
| | - Kuan-Ting Wu
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (J.-H.C.); (W.-Y.C.); (K.-T.W.); (S.-W.J.); (S.-L.H.)
- Department of Orthopedic Surgery, Sports Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
| | - Shun-Wun Jhan
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (J.-H.C.); (W.-Y.C.); (K.-T.W.); (S.-W.J.); (S.-L.H.)
- Department of Orthopedic Surgery, Sports Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
| | - Shan-Ling Hsu
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (J.-H.C.); (W.-Y.C.); (K.-T.W.); (S.-W.J.); (S.-L.H.)
- Department of Orthopedic Surgery, Sports Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
| | - Yi-No Wu
- School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan;
| | - Hou-Tsung Chen
- Department of Orthopedic Surgery, Sports Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
- Department of Leisure and Sports Management, Cheng-Shiu University, Kaohsiung 833, Taiwan
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11
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Dutta S, Ruden DM. Heavy Metals in Umbilical Cord Blood: Effects on Epigenetics and Child Development. Cells 2024; 13:1775. [PMID: 39513881 PMCID: PMC11544782 DOI: 10.3390/cells13211775] [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: 09/05/2024] [Revised: 10/24/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024] Open
Abstract
Heavy metals like arsenic, mercury, cadmium, and lead are harmful pollutants that can change how our genes are regulated without altering the DNA sequence, specifically through a process called DNA methylation (DNAm) at 5-methylcytosine, an epigenetic mark that we will focus on in this review. These changes in DNAm are most sensitive during pregnancy, a critical time for development when these modifications can affect how traits are expressed. Historically, most research on these environmental effects has focused on adults, but now there is more emphasis on studying the impacts during early development and childhood. The placenta acts as a protective barrier between the mother and the baby, and by examining it, scientists can identify changes in key genes that might affect long-term health. This review looks at how exposure to heavy metals during pregnancy can cause changes in the gene regulation by DNAm in newborns, as seen in their umbilical cord blood. These changes reflect the baby's genetic state during pregnancy and can be influenced by the mother's environment and genetics, as well as the baby's own genetics.
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Affiliation(s)
- Sudipta Dutta
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA;
| | - Douglas M. Ruden
- C. S. Mott Center for Human Health and Development, Department of Obstetrics and Gynecology, Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USA
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12
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Cheng J, Zhang C. Mesenchymal Stem Cell Therapy: Therapeutic Opportunities and Challenges for Diabetic Kidney Disease. Int J Mol Sci 2024; 25:10540. [PMID: 39408867 PMCID: PMC11477055 DOI: 10.3390/ijms251910540] [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: 09/04/2024] [Revised: 09/26/2024] [Accepted: 09/28/2024] [Indexed: 10/20/2024] Open
Abstract
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD), which severely affects the quality of patients' lives. However, the current therapeutic approaches can only postpone its progression to ESRD. It is therefore imperative to develop a novel therapeutic strategy for renal injury in DKD, with the objective of restoring renal function and reversing the process of ESRD. In recent years, the potential of mesenchymal stem cell (MSC) therapy for DKD has garnered increasing attention within the scientific community. Preclinical research on MSC therapy has yielded promising results, and the safety of MSC treatment in vivo has been substantiated in clinical studies. An increasing body of evidence suggests that MSC therapy has significant potential for the treatment of DKD. This article reviews the existing research on MSCs and their derived exosomes in treating DKD and analyzes the underlying mechanism of MSC-based therapy for DKD. Additionally, we discuss the potential of combining MSC therapy with conventional pharmacological treatments, along with the constraints and prospects of MSC therapy for DKD. We hope this review can provide a precise and comprehensive understanding of MSCs for the treatment of DKD.
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Affiliation(s)
| | - Chun Zhang
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China;
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13
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Safwan M, Bourgleh MS, Aldoush M, Haider KH. Tissue-source effect on mesenchymal stem cells as living biodrugs for heart failure: Systematic review and meta-analysis. World J Cardiol 2024; 16:469-483. [PMID: 39221190 PMCID: PMC11362808 DOI: 10.4330/wjc.v16.i8.469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 06/24/2024] [Accepted: 07/23/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs), as living biodrugs, have entered advanced phases of clinical assessment for cardiac function restoration in patients with myocardial infarction and heart failure. While MSCs are available from diverse tissue sources, bone-marrow-derived MSCs (BM-MSCs) remain the most well-studied cell type, besides umbilical-cord-derived MSCs (UC-MSCs). The latter offers advantages, including noninvasive availability without ethical considerations. AIM To compare the safety and efficacy of BM-MSCs and UC-MSCs in terms of left ventricular ejection fraction (LVEF), 6-min walking distance (6MWD), and major adverse cardiac events (MACEs). METHODS Five databases were systematically searched to identify randomized controlled trials (RCTs). Thirteen RCTs (693 patients) were included using predefined eligibility criteria. Weighted mean differences and odds ratio (OR) for the changes in the estimated treatment effects. RESULTS UC-MSCs significantly improved LVEF vs controls by 5.08% [95% confidence interval (CI): 2.20%-7.95%] at 6 mo and 2.78% (95%CI: 0.86%-4.70%) at 12 mo. However, no significant effect was observed for BM-MSCs vs controls. No significant changes were observed in the 6MWD with either of the two cell types. Also, no differences were observed for MACEs, except rehospitalization rates, which were lower only with BM-MSCs (odds ratio 0.48, 95%CI: 0.24-0.97) vs controls. CONCLUSION UC-MSCs significantly improved LVEF compared with BM-MSCs. Their advantageous characteristics position them as a promising alternative to MSC-based therapy.
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Affiliation(s)
- Moaz Safwan
- Department of Basic Sciences, Sulaiman Al Rajhi University, Al Bukairiyah 51941, Saudi Arabia
| | - Mariam Safwan Bourgleh
- Department of Basic Sciences, Sulaiman Al Rajhi University, Al Bukairiyah 51941, Saudi Arabia
| | - Mohamed Aldoush
- Department of Basic Sciences, Sulaiman Al Rajhi University, Al Bukairiyah 51941, Saudi Arabia
| | - Khawaja Husnain Haider
- Department of Basic Sciences, Sulaiman Al Rajhi University, Al Bukairiyah 51941, Saudi Arabia.
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14
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Patel AA, Mohamed AH, Rizaev J, Mallick AK, Qasim MT, Abdulmonem WA, Jamal A, Hattiwale HM, Kamal MA, Ahmad F. Application of mesenchymal stem cells derived from the umbilical cord or Wharton's jelly and their extracellular vesicles in the treatment of various diseases. Tissue Cell 2024; 89:102415. [PMID: 38851032 DOI: 10.1016/j.tice.2024.102415] [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: 02/13/2024] [Revised: 04/26/2024] [Accepted: 05/20/2024] [Indexed: 06/10/2024]
Abstract
Mesenchymal stem cells (MSCs) originating from the umbilical cord (UC) or Wharton's jelly (WJ) have attracted substantial interest due to their potential to augment therapeutic approaches for a wide range of disorders. These cells demonstrate a wide range of capabilities in the process of differentiating into a multitude of cell types. Additionally, they possess a significant capacity for proliferation and are conveniently accessible. Furthermore, they possess a status of being immune-privileged, exhibit minimal tumorigenic characteristics, and raise minimal ethical concerns. Consequently, they are well-suited candidates for tissue regeneration and the treatment of diseases. Additionally, UC-derived MSCs offer a substantial yield compared to other sources. The therapeutic effects of these MSCs are closely associated with the release of nanosized extracellular vesicles (EVs), including exosomes and microvesicles (MVs), containing lipids, microRNAs, and proteins that facilitate intercellular communication. Due to their reduced tumorigenic and immunogenic characteristics, in addition to their convenient manipulability, EVs have arisen as a viable alternative for the management of disorders. The favorable characteristics of UC-MSCs or WJ-MSCs and their EVs have generated significant attention in clinical investigations encompassing diverse pathologies. Therefore, we present a review encompassing current preclinical and clinical investigations, examining the implications of UC-MSCs in diverse diseases, including those affecting bone, cartilage, skin, liver, kidney, neural, lung, cardiovascular, muscle, and retinal tissues, as well as conditions like cancer, diabetes, sepsis, and others.
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Affiliation(s)
- Ayyub Ali Patel
- Clinical Biochemistry Department, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Asma'a H Mohamed
- Biomedical Engineering Department, College of Engineering and Technologies, Al-Mustaqbal University, Hilla, Babil 51001, Iraq.
| | - Jasur Rizaev
- Department of Public Health and Healthcare management, Rector, Samarkand State Medical University, 18, Amir Temur Street, Samarkand, Uzbekistan
| | - Ayaz Khurram Mallick
- Clinical Biochemistry Department, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Maytham T Qasim
- College of Health and Medical Technology, Al-Ayen University, Thi-Qar 64001, Iraq
| | - Waleed Al Abdulmonem
- Department of Pathology, College of Medicine, Qassim University, Buraidah, Saudi Arabia
| | - Azfar Jamal
- Department of Biology, College of Science Al-Zulfi, Majmaah University, Al-Majmaah 11952, Saudi Arabia; Health and Basic Science Research Centre, Majmaah University, Al-Majmaah 11952, Saudi Arabia
| | - Haroonrashid M Hattiwale
- Department of Basic Medical Sciences, College of Medicine, Majmaah University, Al-Majmaah 11952, Saudi Arabia.
| | - Mohammad Azhar Kamal
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia
| | - Fuzail Ahmad
- College of Applied Sciences, Almaarefa University, Diriya, Riyadh 13713, Saudi Arabia
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15
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Sharma P, Maurya DK. Wharton's jelly mesenchymal stem cells: Future regenerative medicine for clinical applications in mitigation of radiation injury. World J Stem Cells 2024; 16:742-759. [PMID: 39086560 PMCID: PMC11287430 DOI: 10.4252/wjsc.v16.i7.742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/28/2024] [Accepted: 06/24/2024] [Indexed: 07/25/2024] Open
Abstract
Wharton's jelly mesenchymal stem cells (WJ-MSCs) are gaining significant attention in regenerative medicine for their potential to treat degenerative diseases and mitigate radiation injuries. WJ-MSCs are more naïve and have a better safety profile, making them suitable for both autologous and allogeneic transplantations. This review highlights the regenerative potential of WJ-MSCs and their clinical applications in mitigating various types of radiation injuries. In this review, we will also describe why WJ-MSCs will become one of the most probable stem cells for future regenerative medicine along with a balanced view on their strengths and weaknesses. Finally, the most updated literature related to both preclinical and clinical usage of WJ-MSCs for their potential application in the regeneration of tissues and organs will also be compiled.
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Affiliation(s)
- Prashasti Sharma
- Life Sciences, Homi Bhabha National Institute, Mumbai 400094, Maharashtra, India
- Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, Maharashtra, India
| | - Dharmendra Kumar Maurya
- Life Sciences, Homi Bhabha National Institute, Mumbai 400094, Maharashtra, India
- Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, Maharashtra, India.
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16
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Detante O, Legris L, Moisan A, Rome C. Cell Therapy and Functional Recovery of Stroke. Neuroscience 2024; 550:79-88. [PMID: 38013148 DOI: 10.1016/j.neuroscience.2023.11.027] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 11/19/2023] [Accepted: 11/22/2023] [Indexed: 11/29/2023]
Abstract
Stroke is the most common cause of disability. Brain repair mechanisms are often insufficient to allow a full recovery. Stroke damage involve all brain cell type and extracellular matrix which represent the crucial "glio-neurovascular niche" useful for brain plasticity. Regenerative medicine including cell therapies hold great promise to decrease post-stroke disability of many patients, by promoting both neuroprotection and neural repair through direct effects on brain lesion and/or systemic effects such as immunomodulation. Mechanisms of action vary according to each grafted cell type: "peripheral" stem cells, such as mesenchymal stem cells (MSC), can provide paracrine trophic support, and neural stem/progenitor cells (NSC) or neurons can act as direct cells' replacements. Optimal time window, route, and doses are still debated, and may depend on the chosen medicinal product and its expected mechanism such as neuroprotection, delayed brain repair, systemic effects, or graft survival and integration in host network. MSC, mononuclear cells (MNC), umbilical cord stem cells and NSC are the most investigated. Innovative approaches are implemented concerning combinatorial approaches with growth factors and biomaterials such as injectable hydrogels which could protect a cell graft and/or deliver drugs into the post-stroke cavity at chronic stages. Through main publications of the last two decades, we provide in this review concepts and suggestions to improve future translational researches and larger clinical trials of cell therapy in stroke.
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Affiliation(s)
- Olivier Detante
- Univ. Grenoble Alpes, Inserm, U1216, Grenoble Institute Neurosciences, 38000 Grenoble, France; Stroke Unit, Neurology, CHU Grenoble Alpes, CS10217, 38043 Grenoble, France; Axe Neurosciences Cliniques - Innovative Brain Therapies, CHU Grenoble Alpes, 38000 Grenoble, France.
| | - Loic Legris
- Univ. Grenoble Alpes, Inserm, U1216, Grenoble Institute Neurosciences, 38000 Grenoble, France; Stroke Unit, Neurology, CHU Grenoble Alpes, CS10217, 38043 Grenoble, France; Axe Neurosciences Cliniques - Innovative Brain Therapies, CHU Grenoble Alpes, 38000 Grenoble, France.
| | - Anaick Moisan
- Axe Neurosciences Cliniques - Innovative Brain Therapies, CHU Grenoble Alpes, 38000 Grenoble, France; Cell Therapy and Engineering Unit, EFS Rhône Alpes, 464 route de Lancey, 38330 Saint Ismier, France.
| | - Claire Rome
- Univ. Grenoble Alpes, Inserm, U1216, Grenoble Institute Neurosciences, 38000 Grenoble, France; Stroke Unit, Neurology, CHU Grenoble Alpes, CS10217, 38043 Grenoble, France; Axe Neurosciences Cliniques - Innovative Brain Therapies, CHU Grenoble Alpes, 38000 Grenoble, France.
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17
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Goushki MA, Kharat Z, Kehtari M, Sohi AN, Ahvaz HH, Rad I, HosseinZadeh S, Kouhkan F, Kabiri M. Applications of extraembryonic tissue-derived cells in vascular tissue regeneration. Stem Cell Res Ther 2024; 15:205. [PMID: 38982541 PMCID: PMC11234723 DOI: 10.1186/s13287-024-03784-3] [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: 02/29/2024] [Accepted: 06/06/2024] [Indexed: 07/11/2024] Open
Abstract
Vascular tissue engineering is a promising approach for regenerating damaged blood vessels and developing new therapeutic approaches for heart disease treatment. To date, different sources of cells have been recognized that offer assistance within the recovery of heart supply routes and veins with distinctive capacities and are compelling for heart regeneration. However, some challenges still remain that need to be overcome to establish the full potential application of these cells. In this paper, we review the different cell sources used for vascular tissue engineering, focusing on extraembryonic tissue-derived cells (ESCs), and elucidate their roles in cardiovascular disease. In addition, we highlight the intricate interplay between mechanical and biochemical factors in regulating mesenchymal stem cell (MSC) differentiation, offering insights into optimizing their application in vascular tissues.
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Affiliation(s)
- Mehdi Amiri Goushki
- Department of Life Science Engineering, Faculty of New Sciences & Technologies, University of Tehran, Tehran, 14395-1561, Iran
| | - Zahra Kharat
- Department of Life Science Engineering, Faculty of New Sciences & Technologies, University of Tehran, Tehran, 14395-1561, Iran
| | - Mousa Kehtari
- School of Biology, College of Sciences, University of Tehran, Tehran, 1417614411, Iran
| | - Alireza Naderi Sohi
- National Institute of Genetic Engineering and Biotechnology, Tehran, 1497716316, Iran
| | | | - Iman Rad
- Stem Cell Technology Research Center, Tehran, 15856-36473, Iran
| | - Simzar HosseinZadeh
- Department of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Kouhkan
- Stem Cell Technology Research Center, Tehran, 15856-36473, Iran
| | - Mahboubeh Kabiri
- Department of Biotechnology, College of Science, University of Tehran, Tehran, 14155-6455, Iran.
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18
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Xu X, Chen H, Qiu Y, Chen Y, Liu J, Zeng B, Lin L, Lin X, Zhang L, Zhang L. Intravenous application of human umbilical cord mesenchymal stem cells alleviate neuropathic pain by suppressing microglia activation in rats. Heliyon 2024; 10:e32689. [PMID: 38994051 PMCID: PMC11237945 DOI: 10.1016/j.heliyon.2024.e32689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 05/23/2024] [Accepted: 06/06/2024] [Indexed: 07/13/2024] Open
Abstract
Objective Neuropathic pain has been considered as one of the most serious chronic pain subtypes and causes intolerable suffering to patients physically and mentally. This study aimed to verify the analgesic effect of intravenous administration of human umbilical cord mesenchymal stem cells (HUC-MSCs) upon rats with chronic constriction injury (CCI)-induced neuropathic pain and the concomitant mechanism via modulating microglia. Methods 30 male SD rats were randomized divided into three groups (n = 10 per group): Sham + Saline group (S&S group), CCI + Saline group (C&S group) and CCI + HUC-MSCs group (C&U group). Rats were injected with either saline or HUC-MSCs via the caudal vein on the 7th day after modelling. The paw mechanical withdrawal threshold (PMWT) and thermal withdrawal latency (TWL) of the ligation side were measured before (day 0) and after (day 1, 3, 5, 7, 9, 11, 13, and 15) modelling. On day 15 after modelling, western-blotting and immunofluorescent staining were used to assess the expressive abundance of Iba-1 (a typical biomarker of activated microglia) in the ligation side of the spinal cord dorsal horn, and ultrastructural changes of the ligation of sciatic nerve were evaluated by transmission electron microscope (TEM). Results Compared with the S&S group, PMWT and TWL in the C&S group were significantly decreased on day 5 and then persisted to day 15 after modelling (C&S vs S&S, P < 0.05), while a significant amelioration of mechanical hyperalgesia (day 13, day 15) and thermal allodynia (day 9, day 11, day 15) was observed in the C&U group (C&U vs C&S, P < 0.05). Meanwhile, the expression of Iba-1 was significantly suppressed by systemic infusion of HUC-MSCs in the C&U group according to western-blotting and immunofluorescent staining analyses (P < 0.05). With the aid of TEM detection, we intuitively noticed the efficacious reconstruction of the laminate structure of the sciatic nerve ligation, elimination of mitochondrial swelling, and formation of new myelination were noted on day 15 after modelling in the C&U group. Conclusions Overall, intravenous administration of HUC-MSCs systemically revealed an ameliorative effect upon CCI-induced neuropathic pain in SD rats by inhibiting microglia activation in the dorsal horn of the impaired spinal cord and alleviating sciatic nerve injury. Our findings supply new references for the further development of HUC-MSCs-based cytotherapy for neuropathic pain administration.
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Affiliation(s)
- Xiaodong Xu
- Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, 350000, China
- The Graduate School of Fujian Medical University, Fuzhou, 350000, China
| | - Hui Chen
- Department of Anesthesiology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, 361015, China
| | - Yubei Qiu
- School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350002, China
| | - Ye Chen
- Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, 350000, China
- The Graduate School of Fujian Medical University, Fuzhou, 350000, China
| | - Junle Liu
- Department of Anesthesiology, Xiamen Third Hospital, Xiamen, 361100, China
| | - Bangwei Zeng
- Administration Department of Nosocomial Infection, Fujian Medical University Union Hospital, Fuzhou, 350000, China
| | - Lei Lin
- Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, 350000, China
| | - Xinyan Lin
- Xiamen Public Security Bureau, Xiamen, 361104, China
| | - Leisheng Zhang
- National Health Commission (NHC) Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, 730000, China
- Ji'nan Key Laboratory of Medical Cell Bioengineering, Science and Technology Innovation Center, The Fourth People's Hospital of Jinan, The Teaching Hospital of Shandong First Medical University, Jinan, 250031, China
| | - Liangcheng Zhang
- Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, 350000, China
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19
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Ali FEM, Ibrahim IM, Althagafy HS, Hassanein EHM. Role of immunotherapies and stem cell therapy in the management of liver cancer: A comprehensive review. Int Immunopharmacol 2024; 132:112011. [PMID: 38581991 DOI: 10.1016/j.intimp.2024.112011] [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: 02/02/2024] [Revised: 04/01/2024] [Accepted: 04/02/2024] [Indexed: 04/08/2024]
Abstract
Liver cancer (LC) is the sixth most common disease and the third most common cause of cancer-related mortality. The WHO predicts that more than 1 million deaths will occur from LC by 2030. Hepatocellular carcinoma (HCC) is a common form of primary LC. Today, the management of LC involves multiple disciplines, and multimodal therapy is typically selected on an individual basis, considering the intricate interactions between the patient's overall health, the stage of the tumor, and the degree of underlying liver disease. Currently, the treatment of cancers, including LC, has undergone a paradigm shift in the last ten years because of immuno-oncology. To treat HCC, immune therapy approaches have been developed to enhance or cause the body's natural immune response to specifically target tumor cells. In this context, immune checkpoint pathway inhibitors, engineered cytokines, adoptive cell therapy, immune cells modified with chimeric antigen receptors, and therapeutic cancer vaccines have advanced to clinical trials and offered new hope to cancer patients. The outcomes of these treatments are encouraging. Additionally, treatment using stem cells is a new approach for restoring deteriorated tissues because of their strong differentiation potential and capacity to release cytokines that encourage cell division and the formation of blood vessels. Although there is no proof that stem cell therapy works for many types of cancer, preclinical research on stem cells has shown promise in treating HCC. This review provides a recent update regarding the impact of immunotherapy and stem cells in HCC and promising outcomes.
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Affiliation(s)
- Fares E M Ali
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt; Michael Sayegh, Faculty of Pharmacy, Aqaba University of Technology, Aqaba 77110, Jordan.
| | - Islam M Ibrahim
- Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt
| | - Hanan S Althagafy
- Department of Biochemistry, Faculty of Science, University of Jeddah, Jeddah, Saudi Arabia
| | - Emad H M Hassanein
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt
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20
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Subramanian A, Ip CHL, Qin W, Liu X, W D Carter S, Oguz G, Ramasamy A, E Illanes S, Biswas A, G Perron G, L Fee E, W L Li S, K Y Seah M, A Choolani M, W Kemp M. Simulated lunar microgravity transiently arrests growth and induces osteocyte-chondrocyte lineage differentiation in human Wharton's jelly stem cells. NPJ Microgravity 2024; 10:51. [PMID: 38704360 PMCID: PMC11069510 DOI: 10.1038/s41526-024-00397-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 04/08/2024] [Indexed: 05/06/2024] Open
Abstract
Human Wharton's jelly stem cells (hWJSCs) are multipotent stem cells that are extensively employed in biotechnology applications. However, the impact of simulated lunar microgravity (sμG) on the growth, differentiation, and viability of this cell population is incompletely characterized. We aimed to determine whether acute (72 h) exposure to sμG elicited changes in growth and lineage differentiation in hWJSCs and if putative changes were maintained once exposure to terrestrial gravity (1.0 G) was restored. hWJSCs were cultured under standard 1.0 G conditions prior to being passaged and cultured under sμG (0.16 G) using a random positioning machine. Relative to control, hWJSCs cultured under sμG exhibited marked reductions in growth but not viability. Cell population expression of characteristic stemness markers (CD 73, 90, 105) was significantly reduced under sμG conditions. hWJSCs had 308 significantly upregulated and 328 significantly downregulated genes when compared to 1.0 G culture conditions. Key markers of cell replication, including MKI67, were inhibited. Significant upregulation of osteocyte-chondrocyte lineage markers, including SERPINI1, MSX2, TFPI2, BMP6, COMP, TMEM119, LUM, HGF, CHI3L1 and SPP1, and downregulation of cell fate regulators, including DNMT1 and EZH2, were detected in sμG-exposed hWJSCs. When returned to 1.0 G for 3 days, sμG-exposed hWJSCs had accelerated growth, and expression of stemness markers increased, approaching normal (i.e. 95%) levels. Our data support earlier findings that acute sμG significantly reduces the cell division potential of hWJSCs and suggest that acute sμG-exposure induces reversible changes in cell growth accompanied by osteocyte-chondrocyte changes in lineage differentiation.
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Affiliation(s)
- Arjunan Subramanian
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
| | - Chelsea Han Lin Ip
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
| | - Wei Qin
- Department of Obstetrics and Gynecology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, No. 46 Chongxin Road, 541002, Guilin City, Guangxi Zhuang Autonomous Region, P. R. China
| | - Xiawen Liu
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University, 511436, Guangzhou, P.R. China
| | - Sean W D Carter
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
| | - Gokce Oguz
- Genome Institute of Singapore (GIS). Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome #02-01, Singapore, 138632, Republic of Singapore
| | - Adaikalavan Ramasamy
- Genome Institute of Singapore (GIS). Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome #02-01, Singapore, 138632, Republic of Singapore
| | - Sebastian E Illanes
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universidad de los Andes, Santiago, 7620001, Chile
- IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile
| | - Arijit Biswas
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
- Department of Obstetrics and Gynaecology, National University Hospital, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
| | - Gabriel G Perron
- Center for Genomics and Systems Biology, New York University, New York, NY, 10003, USA
| | - Erin L Fee
- Division of Obstetrics and Gynaecology, University of Western Australia, Perth, WA, Australia
- Women and Infants Research Foundation, King Edward Memorial Hospital, Subiaco, WA, Australia
| | - Sarah W L Li
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
- Department of Obstetrics and Gynaecology, National University Hospital, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
| | - Michelle K Y Seah
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
| | - Mahesh A Choolani
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore.
- Department of Obstetrics and Gynaecology, National University Hospital, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore.
| | - Matthew W Kemp
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore.
- Department of Obstetrics and Gynaecology, National University Hospital, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore.
- Division of Obstetrics and Gynaecology, University of Western Australia, Perth, WA, Australia.
- Women and Infants Research Foundation, King Edward Memorial Hospital, Subiaco, WA, Australia.
- Centre for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, 980-8574, Japan.
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21
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Jeong SY, Park BW, Kim J, Lee S, You H, Lee J, Lee S, Park JH, Kim J, Sim W, Ban K, Park J, Park HJ, Kim S. Hyaluronic acid stimulation of stem cells for cardiac repair: a cell-free strategy for myocardial infarct. J Nanobiotechnology 2024; 22:149. [PMID: 38570846 PMCID: PMC10993512 DOI: 10.1186/s12951-024-02410-x] [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: 10/26/2023] [Accepted: 03/18/2024] [Indexed: 04/05/2024] Open
Abstract
BACKGROUND Myocardial infarction (MI), a representative form of ischemic heart disease, remains a huge burden worldwide. This study aimed to explore whether extracellular vesicles (EVs) secreted from hyaluronic acid (HA)-primed induced mesenchymal stem cells (HA-iMSC-EVs) could enhance the cardiac repair after MI. RESULTS HA-iMSC-EVs showed typical characteristics for EVs such as morphology, size, and marker proteins expression. Compared with iMSC-EVs, HA-iMSC-EVs showed enhanced tube formation and survival against oxidative stress in endothelial cells, while reduced reactive oxygen species (ROS) generation in cardiomyocytes. In THP-1 macrophages, both types of EVs markedly reduced the expression of pro-inflammatory signaling players, whereas HA-iMSC-EVs were more potent in augmenting anti-inflammatory markers. A significant decrease of inflammasome proteins was observed in HA-iMSC-EV-treated THP-1. Further, phospho-SMAD2 as well as fibrosis markers in TGF-β1-stimulated cardiomyocytes were reduced in HA-iMSC-EVs treatment. Proteomic data showed that HA-iMSC-EVs were enriched with multiple pathways including immunity, extracellular matrix organization, angiogenesis, and cell cycle. The localization of HA-iMSC-EVs in myocardium was confirmed after delivery by either intravenous or intramyocardial route, with the latter increased intensity. Echocardiography revealed that intramyocardial HA-iMSC-EVs injections improved cardiac function and reduced adverse cardiac remodeling and necrotic size in MI heart. Histologically, MI hearts receiving HA-iMSC-EVs had increased capillary density and viable myocardium, while showed reduced fibrosis. CONCLUSIONS Our results suggest that HA-iMSC-EVs improve cardiac function by augmenting vessel growth, while reducing ROS generation, inflammation, and fibrosis in MI heart.
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Affiliation(s)
- Seon-Yeong Jeong
- Brexogen Research Center, Brexogen Inc., Songpa‑gu, Seoul, 05855, South Korea
| | - Bong-Woo Park
- Department of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo-daero, Seoho-gu, Seoul, 06591, Republic of Korea
- Catholic High-Performance Cell Therapy Center and Department of Medical Life Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seoho-gu, Seoul, 06591, Republic of Korea
| | - Jimin Kim
- Brexogen Research Center, Brexogen Inc., Songpa‑gu, Seoul, 05855, South Korea
| | - Seulki Lee
- Brexogen Research Center, Brexogen Inc., Songpa‑gu, Seoul, 05855, South Korea
| | - Haedeun You
- Brexogen Research Center, Brexogen Inc., Songpa‑gu, Seoul, 05855, South Korea
| | - Joohyun Lee
- Brexogen Research Center, Brexogen Inc., Songpa‑gu, Seoul, 05855, South Korea
| | - Susie Lee
- Department of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo-daero, Seoho-gu, Seoul, 06591, Republic of Korea
| | - Jae-Hyun Park
- Department of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo-daero, Seoho-gu, Seoul, 06591, Republic of Korea
| | - Jinju Kim
- Department of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo-daero, Seoho-gu, Seoul, 06591, Republic of Korea
| | - Woosup Sim
- Department of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo-daero, Seoho-gu, Seoul, 06591, Republic of Korea
| | - Kiwon Ban
- Department of Biomedical Science, City University of Hong Kong, Kowloon Tong, Hong Kong
| | - Joonghoon Park
- Graduate School of International Agricultural Technology, Institutes of Green-Bio Science and Technology, Seoul National University, Pyeongchang, Gangwon-do, 25354, South Korea
| | - Hun-Jun Park
- Department of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo-daero, Seoho-gu, Seoul, 06591, Republic of Korea.
- Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
| | - Soo Kim
- Brexogen Research Center, Brexogen Inc., Songpa‑gu, Seoul, 05855, South Korea.
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22
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Nikzad S, Same S, Safiri S, Dolati S, Roushangar Zineh B, Meshgi S, Roshangar L, Şahin F. The effect of Wharton's jelly-derived stem cells seeded/boron-loaded acellular scaffolds on the healing of full-thickness burn wounds in the rat model. Biomed Mater 2024; 19:025042. [PMID: 38364284 DOI: 10.1088/1748-605x/ad2a3e] [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: 06/19/2023] [Accepted: 02/16/2024] [Indexed: 02/18/2024]
Abstract
Burn wounds are the most destructive and complicated type of skin or underlying soft tissue injury that are exacerbated by a prolonged inflammatory response. Several cell-based therapeutic systems through the culturing of potent stem cells on modified scaffolds have been developed to direct the burn healing challenges. In this context, a new regenerative platform based on boron (B) enriched-acellular sheep small intestine submucosa (AOSIS) scaffold was designed and used as a carrier for mesenchymal stem cells derived from Wharton's jelly (WJMSCs) aiming to promote the tissue healing in burn-induced rat models. hWJMSCs have been extracted from human extra-embryonic umbilical cord tissue. Thereafter, 96 third-degree burned Wistar male rats were divided into 4 groups. The animals that did not receive any treatment were considered as group A (control). Then, group B was treated just by AOSIS scaffold, group C was received cell-seeded AOSIS scaffold (hWJMSCs-AOSIS), and group D was covered by boron enriched-cell-AOSIS scaffold (B/hWJMSCs-AOSIS). Inflammatory factors, histopathological parameters, and the expression levels of epitheliogenic and angiogenic proteins were assessed on 5, 14 and 21 d post-wounding. Application of the B/hWJMSCs-AOSIS on full-thickness skin-burned wounds significantly reduced the volume of neutrophils and lymphocytes at day 21 post-burning, whilst the number of fibroblasts and blood vessels enhanced at this time. In addition, molecular and histological analysis of wounds over time further verified that the addition of boron promoted wound healing, with decreased inflammatory factors, stimulated vascularization, accelerated re-epithelialization, and enhanced expression levels of epitheliogenic genes. In addition, the boron incorporation amplified wound closure via increasing collagen deposition and fibroblast volume and activity. Therefore, this newly fabricated hWJMSCs/B-loaded scaffold can be used as a promising system to accelerate burn wound reconstruction through inflammatory regulation and angiogenesis stimulation.
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Affiliation(s)
- Sadeneh Nikzad
- Biology Department, Concordia University, Montreal, Canada
| | - Saeideh Same
- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saeid Safiri
- Neurosciences Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sanam Dolati
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Shahla Meshgi
- General Cardiologist, Tabriz Madani Heart Hospital, Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Roshangar
- Faculty of Medicine, Department of Anatomical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fikrettin Şahin
- Faculty of Engineering and Architecture, Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey
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Namestnikova DD, Kovalenko DB, Pokusaeva IA, Chudakova DA, Gubskiy IL, Yarygin KN, Baklaushev VP. Mesenchymal stem cells in the treatment of ischemic stroke. КЛИНИЧЕСКАЯ ПРАКТИКА 2024; 14:49-64. [DOI: 10.17816/clinpract624157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/07/2025] Open
Abstract
Over the past two decades, multiple preclinical studies have shown that transplantation of mesenchymal stem cells leads to a pronounced positive effect in animals with experimental stroke. Based on the promising results of preclinical studies, several clinical trials on the transplantation of mesenchymal stem cells to stroke patients have also been conducted. In this review, we present and analyze the results of completed clinical trials dedicated to the mesenchymal stem cells transplantation in patients with ischemic stroke. According to the obtained results, it can be concluded that transplantation of mesenchymal stem cells is safe and feasible from the economic and biomedical point of view. For the further implementa-tion of this promising approach into the clinical practice, randomized, placebo-controlled, multicenter clinical trials are needed with a large sample of patients and optimized cell transplantation protocols and patient inclusion criteria. In this review we also discuss possi-ble strategies to enhance the effectiveness of cell therapy with the use of mesenchymal stem cells.
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Affiliation(s)
- Daria D. Namestnikova
- Federal Center of Brain Research and Neurotechnologies
- Pirogov Russian National Research Medical University
| | | | | | | | - Ilya L. Gubskiy
- Federal Center of Brain Research and Neurotechnologies
- Pirogov Russian National Research Medical University
| | | | - Vladimir P. Baklaushev
- Federal Center of Brain Research and Neurotechnologies
- Pirogov Russian National Research Medical University
- Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of the Federal Medical Biological Agency
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24
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Shafaf T, Kazeminejad SR, Hoveizi E. Evaluation of lncRNA Expression During the Differentiation of Mesenchymal Stem Cells to Insulin-Secreting Progenitors. Mol Neurobiol 2024; 61:372-384. [PMID: 37610615 DOI: 10.1007/s12035-023-03571-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 08/10/2023] [Indexed: 08/24/2023]
Abstract
Diabetes mellitus is a metabolic disease caused by a defect in insulin secretion, insulin function, or both that destroys pancreatic islet beta cells. There is ample evidence that long non-coding RNAs (lncRNAs) play a vital role in cell formation and differentiation. The present study aims to investigate the expression pattern of specific lncRNAs in mesenchymal stem cell (MSC) differentiation into insulin-producing beta cell (IPCs) progenitors for cell therapy purposes. MSCs were extracted from human umbilical cord Wharton jelly (hWJ-MSCs) using the explant method and cultured in two-dimensional (2D) and three-dimensional (3D) media on polylactic acid/Wax (PLA/Wax) nanofibrous scaffold using a three-step protocol containing CHIR99021 small molecules and Indolactam V. At the end of each differentiation step, immunocytochemistry and qRT-PCR were used to confirm the differentiation at the protein and RNA levels and the expression changes of six selective lncRNAs were evaluated by qRT-PCR. The results indicated that the expression of the selected lncRNAs was significantly altered during the differentiation process into beta progenitor cells, indicating their potential role in regulating the IPC differentiation process. More specifically, all of the desired lncRNAs demonstrated a significant increase during the beta cell differentiation, with HI-LNC71 and HI-LNA12 experiencing the highest expression in the produced Beta cell progenitors respectively (p<0.0001). These results can be valuable in tissue engineering and treatment studies by replacing beta precursor cells to control diabetic patients.
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Affiliation(s)
- Tina Shafaf
- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Sayed Reza Kazeminejad
- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Elham Hoveizi
- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
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25
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Jeyaraman M, Nallakumarasamy A, Jeyaraman N, Ramasubramanian S. Tissue engineering in chondral defect. COMPUTATIONAL BIOLOGY FOR STEM CELL RESEARCH 2024:361-378. [DOI: 10.1016/b978-0-443-13222-3.00033-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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26
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Arjmand B, Rezaei-Tavirani M, Alavi-Moghadam S, Tayanloo-Beik A, Gholami M, Kokabi-Hamidpour S, Arjmand R, Rezazadeh-Mafi A, Mohamadi-Jahani F, Larijani B. Standard Operating Procedure for Production of Mouse Brown Adipose Tissue-Derived Mesenchymal Stem Cells. Methods Mol Biol 2024; 2736:115-125. [PMID: 36515894 DOI: 10.1007/7651_2022_468] [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] [Indexed: 12/15/2022]
Abstract
Over the past years, stem cell technology was heralded as a significant breakthrough of the century in scrutinizing the intricacies of human body biology and discovering different therapeutic approaches. Recently, adipose tissue, as a suitable source of harvesting mesenchymal stem cells, has attracted the attention of many researchers in the field of regenerative medicine. Adipose tissue-derived mesenchymal stem cells can self-renew and differentiate into different types of cells such as adipocytes, chondrocytes, and osteoblasts. Adipose tissue, especially brown type, is considered an attractive cell source for various therapeutic purposes, such as restoring damaged tissue or fighting against diseases such as obesity. The growth of importance of stem cell applications in regenerative medicine has highlighted the need to seek appropriate mesenchymal stem cells sources. Recently, in the light of many efforts in the field of regenerative medicine, mice have gained increasing interest as a suitable source of adipose tissue for the extraction of mesenchymal stem cells, which can be used in the preclinical investigations in order to aid in the treatment of many human diseases.
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Affiliation(s)
- Babak Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | | | - Sepideh Alavi-Moghadam
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Akram Tayanloo-Beik
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahdi Gholami
- Department of Toxicology & Pharmacology, Faculty of Pharmacy; Toxicology and Poisoning Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Shayesteh Kokabi-Hamidpour
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Rasta Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Rezazadeh-Mafi
- Clinical Oncologist, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereshteh Mohamadi-Jahani
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical sciences, Tehran, Iran
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Zhang H, Gu Y, Zhang K, Tu Y, Ouyang C. Roles and mechanisms of umbilical cord mesenchymal stem cells in the treatment of diabetic foot: A review of preclinical and clinical studies. J Diabetes Complications 2024; 38:108671. [PMID: 38154217 DOI: 10.1016/j.jdiacomp.2023.108671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 11/29/2023] [Accepted: 12/17/2023] [Indexed: 12/30/2023]
Abstract
AIMS Growing preclinical and clinical evidence has suggested the potential method of umbilical cord mesenchymal stem cell (UCMSC) therapy for diabetic foot. Thus, the authors provided an outline of the application of UCMSCs in the treatment of diabetic foot and further summarized the roles and mechanisms of this therapy. DATA SYNTHESIS With no time limitations, the authors searched the Web of Science, Cochrane Central Register of Controlled Trials, and PubMed (MEDLINE) databases. 14 studies were included, including 9 preclinical experiments and 5 clinical trials (3 RCTs and 2 single-arm trials). CONCLUSIONS The UCMSCs are of great efficacy and safety, and function mainly by reducing inflammation, regulating immunity, promoting growth factors, and enhancing the functions of vascular endothelial cells, fibroblasts, and keratinocytes. As a result, ulcer healing-related biological processes ensue, which finally lead to diabetic foot ulcer healing and clinical symptom improvement. UCMSC treatment enhances diabetic foot ulcer healing and has a safety profile. They function mainly by modulating immunity, promoting growth factor secretion, and enhancing cellular functions. More well-designed preclinical and clinical studies are needed to provide the most optimal protocol, the comprehensive molecular mechanisms, as well as to further evaluate the efficiency and safety profile of UCMSC treatment in diabetic foot patients.
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Affiliation(s)
- Haorui Zhang
- Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xi Cheng District, Beijing 100037, China
| | - Yuanrui Gu
- Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xi Cheng District, Beijing 100037, China
| | - Ke Zhang
- Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xi Cheng District, Beijing 100037, China
| | - Yanxia Tu
- Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xi Cheng District, Beijing 100037, China
| | - Chenxi Ouyang
- Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xi Cheng District, Beijing 100037, China.
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Zheng ZK, Kong L, Dai M, Chen YD, Chen YH. ADSC-Exos outperform BMSC-Exos in alleviating hydrostatic pressure-induced injury to retinal ganglion cells by upregulating nerve growth factors. World J Stem Cells 2023; 15:1077-1092. [PMID: 38179214 PMCID: PMC10762527 DOI: 10.4252/wjsc.v15.i12.1077] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 11/17/2023] [Accepted: 12/04/2023] [Indexed: 12/26/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) have protective effects on the cornea, lacrimal gland, retina, and photoreceptor cell damage, which may be mediated by exosomes (exos) released by MSCs. AIM To investigate the ameliorating effect of exos derived from different MSCs on retinal ganglion cell (RGC) injury induced by hydrostatic pressure. METHODS The RGC injury model was constructed by RGC damage under different hydrostatic pressures (40, 80, 120 mmHg). Then RGCs were cultured with adipose-derived stem cell (ADSC)-Exos and bone marrow-derived stem cell (BMSC)-Exos. Cell Counting Kit-8, transmission electron microscopy, flow cytometry, immunofluorescence, real-time quantitative polymerase chain reaction, and western blotting were performed to detect the ameliorating effect of exos on pressure-induced RGC injury. RESULTS ADSC-Exos and BMSC-Exos were successfully isolated and obtained. The gibbosity of RGCs was lower, the cells were irregularly ellipsoidal under pressure, and the addition of ADSC-Exos and BMSC-Exos significantly restored RGC morphology. Furthermore, the proliferative activity of RGCs was increased and the apoptosis of RGCs was inhibited. Moreover, the levels of lactate dehydrogenase and apoptosis-related proteins were increased, and the concentrations of antiapoptotic proteins and neurotrophic factors were decreased in damaged RGCs. However, the above indicators were significantly improved after ADSC-Exos and BMSC-Exos treatment. CONCLUSION These findings indicated that ADSC-Exos and BMSC-Exos could ameliorate RGC injury caused by hydrostatic pressure by inhibiting apoptosis and increasing the secretion of neurotrophic factors.
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Affiliation(s)
- Zhi-Kun Zheng
- Department of Ophthalmology, Affiliated Hospital of Yunnan University/Yunnan Eye Hospital, Kunming 650021, Yunnan Province, China
| | - Lei Kong
- Department of Ophthalmology, Affiliated Hospital of Yunnan University/Yunnan Eye Hospital, Kunming 650021, Yunnan Province, China
| | - Min Dai
- Department of Ophthalmology, Affiliated Hospital of Yunnan University/Yunnan Eye Hospital, Kunming 650021, Yunnan Province, China.
| | - Yi-Dan Chen
- Department of Ophthalmology, Affiliated Hospital of Yunnan University/Yunnan Eye Hospital, Kunming 650021, Yunnan Province, China
| | - Yan-Hua Chen
- Department of Ophthalmology, Affiliated Hospital of Yunnan University/Yunnan Eye Hospital, Kunming 650021, Yunnan Province, China
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Sababathy M, Ramanathan G, Abd Rahaman NY, Ramasamy R, Biau FJ, Qi Hao DL, Hamid NFS. A 'one stone, two birds' approach with mesenchymal stem cells for acute respiratory distress syndrome and Type II diabetes mellitus. Regen Med 2023; 18:913-934. [PMID: 38111999 DOI: 10.2217/rme-2023-0193] [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] [Indexed: 12/20/2023] Open
Abstract
This review explores the intricate relationship between acute respiratory distress syndrome (ARDS) and Type II diabetes mellitus (T2DM). It covers ARDS epidemiology, etiology and pathophysiology, along with current treatment trends and challenges. The lipopolysaccharides (LPS) role in ARDS and its association between non-communicable diseases and COVID-19 are discussed. The review highlights the therapeutic potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) for ARDS and T2DM, emphasizing their immunomodulatory effects. This review also underlines how T2DM exacerbates ARDS pathophysiology and discusses the potential of hUC-MSCs in modulating immune responses. In conclusion, the review highlights the multidisciplinary approach to managing ARDS and T2DM, focusing on inflammation, oxidative stress and potential therapy of hUC-MSCs in the future.
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Affiliation(s)
- Mogesh Sababathy
- Department of Veterinary Pathology & Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Ghayathri Ramanathan
- Faculty of Computer Science & Information Technology, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Nor Yasmin Abd Rahaman
- Department of Veterinary Laboratory Diagnostics, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
- Laboratory of Vaccines & Biomolecules, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Rajesh Ramasamy
- Department of Pathology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Foo Jhi Biau
- Centre for Drug Discovery & Molecular Pharmacology (CDDMP), Faculty of Health & Medical Sciences, Taylor's University, Selangor, Subang Jaya, 47500, Malaysia
- School of Pharmacy, Faculty of Health & Medical Sciences, Taylor's University, Selangor, Subang Jaya, 47500, Malaysia
| | - Daniel Looi Qi Hao
- My Cytohealth Sdn. Bhd., 18-2, Jalan Radin Bagus 1, Bandar Seri Petaling, Kuala Lumpur, 57000, Malaysia
| | - Nur-Fazila Saulol Hamid
- Department of Veterinary Pathology & Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
- Laboratory of Vaccines & Biomolecules, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
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Gupta G, Hussain MS, Thapa R, Dahiya R, Mahapatra DK, Bhat AA, Singla N, Subramaniyan V, Rawat S, Jakhmola V, S R, Dua K. Hope on the horizon: Wharton's jelly mesenchymal stem cells in the fight against COVID-19. Regen Med 2023; 18:675-678. [PMID: 37554111 PMCID: PMC10411327 DOI: 10.2217/rme-2023-0077] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 07/19/2023] [Indexed: 08/10/2023] Open
Affiliation(s)
- Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur, India
- Center for Global Health research (CGHR), Saveetha Institute of Medical & Technical Science (SIMATS), Saveetha University, Chennai, India
| | - Md Sadique Hussain
- School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, Jaipur, Rajasthan, India
| | - Riya Thapa
- School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur, India
| | - Rajiv Dahiya
- School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, Saint Augustine, Trinidad & Tobago
| | - Debarshi Kar Mahapatra
- Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune 411018, Maharashtra, India
| | - Asif Ahmad Bhat
- School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur, India
| | - Neelam Singla
- School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur, India
| | - Vetriselvan Subramaniyan
- Department of Pharmacology, Jeffrey Cheah School of Medicine & Health Sciences, MONASH University, Malaysia
| | - Sushama Rawat
- School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, Jaipur, Rajasthan, India
| | - Vikas Jakhmola
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Roshan S
- Deccan School of Pharmacy, Hyderabad, India
| | - Kamal Dua
- Faculty of Health, Australian Research Centre in Complementary & Integrative Medicine, University of Technology, Sydney, Ultimo-NSW 2007, Australia
- Discipline of Pharmacy, Graduate School of Health, University of Technology, Sydney, Ultimo-NSW 2007, Australia
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31
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Ma L, He X, Wu Q. The Molecular Regulatory Mechanism in Multipotency and Differentiation of Wharton's Jelly Stem Cells. Int J Mol Sci 2023; 24:12909. [PMID: 37629090 PMCID: PMC10454700 DOI: 10.3390/ijms241612909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 08/06/2023] [Accepted: 08/10/2023] [Indexed: 08/27/2023] Open
Abstract
Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are isolated from Wharton's jelly tissue of umbilical cords. They possess the ability to differentiate into lineage cells of three germ layers. WJ-MSCs have robust proliferative ability and strong immune modulation capacity. They can be easily collected and there are no ethical problems associated with their use. Therefore, WJ-MSCs have great tissue engineering value and clinical application prospects. The identity and functions of WJ-MSCs are regulated by multiple interrelated regulatory mechanisms, including transcriptional regulation and epigenetic modifications. In this article, we summarize the latest research progress on the genetic/epigenetic regulation mechanisms and essential signaling pathways that play crucial roles in pluripotency and differentiation of WJ-MSCs.
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Affiliation(s)
| | | | - Qiang Wu
- The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China
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32
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Drobiova H, Sindhu S, Ahmad R, Haddad D, Al-Mulla F, Al Madhoun A. Wharton's jelly mesenchymal stem cells: a concise review of their secretome and prospective clinical applications. Front Cell Dev Biol 2023; 11:1211217. [PMID: 37440921 PMCID: PMC10333601 DOI: 10.3389/fcell.2023.1211217] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 06/13/2023] [Indexed: 07/15/2023] Open
Abstract
Accumulating evidence indicates that most primary Wharton's jelly mesenchymal stem cells (WJ-MSCs) therapeutic potential is due to their paracrine activity, i.e., their ability to modulate their microenvironment by releasing bioactive molecules and factors collectively known as secretome. These bioactive molecules and factors can either be released directly into the surrounding microenvironment or can be embedded within the membrane-bound extracellular bioactive nano-sized (usually 30-150 nm) messenger particles or vesicles of endosomal origin with specific route of biogenesis, known as exosomes or carried by relatively larger particles (100 nm-1 μm) formed by outward blebbing of plasma membrane called microvesicles (MVs); exosomes and MVs are collectively known as extracellular vesicles (EVs). The bioactive molecules and factors found in secretome are of various types, including cytokines, chemokines, cytoskeletal proteins, integrins, growth factors, angiogenic mediators, hormones, metabolites, and regulatory nucleic acid molecules. As expected, the secretome performs different biological functions, such as immunomodulation, tissue replenishment, cellular homeostasis, besides possessing anti-inflammatory and anti-fibrotic effects. This review highlights the current advances in research on the WJ-MSCs' secretome and its prospective clinical applications.
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Affiliation(s)
- Hana Drobiova
- Human Genetics Unit, Department of Pathology, College of Medicine, Kuwait University, Jabriya, Kuwait
| | - Sardar Sindhu
- Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman, Kuwait
- Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait
| | - Rasheed Ahmad
- Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait
| | - Dania Haddad
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
| | - Fahd Al-Mulla
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
| | - Ashraf Al Madhoun
- Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman, Kuwait
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
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Pala R, Cruciani S, Manca A, Garroni G, El Faqir MA, Lentini V, Capobianco G, Pantaleo A, Maioli M. Mesenchymal Stem Cell Behavior under Microgravity: From Stress Response to a Premature Senescence. Int J Mol Sci 2023; 24:ijms24097753. [PMID: 37175460 PMCID: PMC10178040 DOI: 10.3390/ijms24097753] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 04/17/2023] [Accepted: 04/20/2023] [Indexed: 05/15/2023] Open
Abstract
Mesenchymal stem cells are undifferentiated cells able to acquire different phenotypes under specific stimuli. Wharton's jelly is a tissue in the umbilical cord that contains mesenchymal stromal cells (MSCs) with a high plasticity and differentiation potential. Their regeneration capability is compromised by cell damage and aging. The main cause of cell damage is oxidative stress coming from an imbalance between oxidant and antioxidant species. Microgravity represents a stressing condition able to induce ROS production, ultimately leading to different subcellular compartment damages. Here, we analyzed molecular programs of stemness (Oct-4; SOX2; Nanog), cell senescence, p19, p21 (WAF1/CIP1), p53, and stress response in WJ-MSCs exposed to microgravity. From our results, we can infer that a simulated microgravity environment is able to influence WJ-MSC behavior by modulating the expression of stress and stemness-related genes, cell proliferation regulators, and both proapoptotic and antiapoptotic genes. Our results suggest a cellular adaptation addressed to survival occurring during the first hours of simulated microgravity, followed by a loss of stemness and proliferation capability, probably related to the appearance of a molecular program of senescence.
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Affiliation(s)
- Renzo Pala
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
| | - Sara Cruciani
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
| | - Alessia Manca
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
| | - Giuseppe Garroni
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
| | - Mohammed Amine El Faqir
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
| | - Veronica Lentini
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
| | - Giampiero Capobianco
- Department of Medical, Surgical and Experimental Sciences, Gynecologic and Obstetric Clinic, University of Sassari, 07100 Sassari, Italy
| | - Antonella Pantaleo
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
| | - Margherita Maioli
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
- Center for Developmental Biology and Reprogramming (CEDEBIOR), Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
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Yu X, Liu P, Li Z, Zhang Z. Function and mechanism of mesenchymal stem cells in the healing of diabetic foot wounds. Front Endocrinol (Lausanne) 2023; 14:1099310. [PMID: 37008908 PMCID: PMC10061144 DOI: 10.3389/fendo.2023.1099310] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
Diabetes has become a global public health problem. Diabetic foot is one of the most severe complications of diabetes, which often places a heavy economic burden on patients and seriously affects their quality of life. The current conventional treatment for the diabetic foot can only relieve the symptoms or delay the progression of the disease but cannot repair damaged blood vessels and nerves. An increasing number of studies have shown that mesenchymal stem cells (MSCs) can promote angiogenesis and re-epithelialization, participate in immune regulation, reduce inflammation, and finally repair diabetic foot ulcer (DFU), rendering it an effective means of treating diabetic foot disease. Currently, stem cells used in the treatment of diabetic foot are divided into two categories: autologous and allogeneic. They are mainly derived from the bone marrow, umbilical cord, adipose tissue, and placenta. MSCs from different sources have similar characteristics and subtle differences. Mastering their features to better select and use MSCs is the premise of improving the therapeutic effect of DFU. This article reviews the types and characteristics of MSCs and their molecular mechanisms and functions in treating DFU to provide innovative ideas for using MSCs to treat diabetic foot and promote wound healing.
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Affiliation(s)
- Xiaoping Yu
- School of Medicine and Nursing, Chengdu University, Chengdu, Sichuan, China
| | - Pan Liu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Zheng Li
- People’s Hospital of Jiulongpo District, Chongqing, China
| | - Zhengdong Zhang
- School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, China
- Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
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Sánchez-Porras D, Durand-Herrera D, Carmona R, Blanco-Elices C, Garzón I, Pozzobon M, San Martín S, Alaminos M, García-García ÓD, Chato-Astrain J, Carriel V. Expression of Basement Membrane Molecules by Wharton Jelly Stem Cells (WJSC) in Full-Term Human Umbilical Cords, Cell Cultures and Microtissues. Cells 2023; 12:cells12040629. [PMID: 36831296 PMCID: PMC9954414 DOI: 10.3390/cells12040629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 02/06/2023] [Accepted: 02/08/2023] [Indexed: 02/17/2023] Open
Abstract
Wharton's jelly stem cells (WJSC) from the human umbilical cord (UC) are one of the most promising mesenchymal stem cells (MSC) in tissue engineering (TE) and advanced therapies. The cell niche is a key element for both, MSC and fully differentiated tissues, to preserve their unique features. The basement membrane (BM) is an essential structure during embryonic development and in adult tissues. Epithelial BMs are well-known, but similar structures are present in other histological structures, such as in peripheral nerve fibers, myocytes or chondrocytes. Previous studies suggest the expression of some BM molecules within the Wharton's Jelly (WJ) of UC, but the distribution pattern and full expression profile of these molecules have not been yet elucidated. In this sense, the aim of this histological study was to evaluate the expression of main BM molecules within the WJ, cultured WJSC and during WJSC microtissue (WJSC-MT) formation process. Results confirmed the presence of a pericellular matrix composed by the main BM molecules-collagens (IV, VII), HSPG2, agrin, laminin and nidogen-around the WJSC within UC. Additionally, ex vivo studies demonstrated the synthesis of these BM molecules, except agrin, especially during WJSC-MT formation process. The WJSC capability to synthesize main BM molecules could offer new alternatives for the generation of biomimetic-engineered substitutes where these molecules are particularly needed.
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Affiliation(s)
- David Sánchez-Porras
- Tissue Engineering Group, Department of Histology, Faculty of Medicine, Universidad de Granada, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- Doctoral Program in Biomedicine, Doctoral School, Universidad de Granada, 18016 Granada, Spain
| | - Daniel Durand-Herrera
- Tissue Engineering Group, Department of Histology, Faculty of Medicine, Universidad de Granada, 18016 Granada, Spain
- Facultad de Odontología, Universidad Michoacana de San Nicolás de Hidalgo (UMSNH), Morelia 58010, Mexico
| | - Ramón Carmona
- Department of Cell Biology, Faculty of Sciences, Universidad de Granada, 18071 Granada, Spain
| | - Cristina Blanco-Elices
- Tissue Engineering Group, Department of Histology, Faculty of Medicine, Universidad de Granada, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
| | - Ingrid Garzón
- Tissue Engineering Group, Department of Histology, Faculty of Medicine, Universidad de Granada, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
| | - Michela Pozzobon
- Department of Women and Children’s Health, University of Padova, 35129 Padova, Italy
- Corso Stati Uniti 4, Institute of Pediatric Research Città della Speranza, 35127 Padova, Italy
| | - Sebastián San Martín
- Centro de Investigaciones Biomédicas, Escuela de Medicina, Facultad de Medicina, Universidad de Valparaíso, Valparaíso 2520000, Chile
| | - Miguel Alaminos
- Tissue Engineering Group, Department of Histology, Faculty of Medicine, Universidad de Granada, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
| | - Óscar Darío García-García
- Tissue Engineering Group, Department of Histology, Faculty of Medicine, Universidad de Granada, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- Correspondence: (Ó.D.G.-G.); (J.C.-A.)
| | - Jesús Chato-Astrain
- Tissue Engineering Group, Department of Histology, Faculty of Medicine, Universidad de Granada, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- Correspondence: (Ó.D.G.-G.); (J.C.-A.)
| | - Víctor Carriel
- Tissue Engineering Group, Department of Histology, Faculty of Medicine, Universidad de Granada, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
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Sung TC, Wang T, Liu Q, Ling QD, Subbiah SK, Renuka RR, Hsu ST, Umezawa A, Higuchi A. Cell-binding peptides on the material surface guide stem cell fate of adhesion, proliferation and differentiation. J Mater Chem B 2023; 11:1389-1415. [PMID: 36727243 DOI: 10.1039/d2tb02601e] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Human cells, especially stem cells, need to communicate and interact with extracellular matrix (ECM) proteins, which not only serve as structural components but also guide and support cell fate and properties such as cell adhesion, proliferation, survival and differentiation. The binding of the cells with ECM proteins or ECM-derived peptides via cell adhesion receptors such as integrins activates several signaling pathways that determine the cell fate, morphological change, proliferation and differentiation. The development of synthetic ECM protein-derived peptides that mimic the biological and biochemical functions of natural ECM proteins will benefit academic and clinical application. Peptides derived from or inspired by specific ECM proteins can act as agonists of each ECM protein receptor. Given that most ECM proteins function in cell adhesion via integrin receptors, many peptides have been developed that bind to specific integrin receptors. In this review, we discuss the peptide sequence, immobilization design, reaction method, and functions of several ECM protein-derived peptides. Various peptide sequences derived from mainly ECM proteins, which are used for coating or grafting on dishes, scaffolds, hydrogels, implants or nanofibers, have been developed to improve the adhesion, proliferation or differentiation of stem cells and to culture differentiated cells. This review article will help to inform the optimal choice of ECM protein-derived peptides for the development of scaffolds, implants, hydrogels, nanofibers and 2D cell culture dishes to regulate the proliferation and direct the differentiation of stem cells into specific lineages.
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Affiliation(s)
- Tzu-Cheng Sung
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan Road, Wenzhou, Zhejiang, 325027, China.
| | - Ting Wang
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan Road, Wenzhou, Zhejiang, 325027, China.
| | - Qian Liu
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan Road, Wenzhou, Zhejiang, 325027, China.
| | - Qing-Dong Ling
- Cathay Medical Research Institute, Cathay General Hospital, No. 32, Ln 160, Jian-Cheng Road, Hsi-Chi City, Taipei 221, Taiwan
| | - Suresh Kumar Subbiah
- Centre for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, 173, Agaram Road, Tambaram East, Chennai-73, 600078, India
| | - Remya Rajan Renuka
- Centre for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, 173, Agaram Road, Tambaram East, Chennai-73, 600078, India
| | - Shih-Tien Hsu
- Department of Internal Medicine, Taiwan Landseed Hospital, 77 Kuangtai Road, Pingjen City, Tao-Yuan County 32405, Taiwan
| | - Akihiro Umezawa
- Department of Reproduction, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan
| | - Akon Higuchi
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan Road, Wenzhou, Zhejiang, 325027, China. .,Department of Chemical and Materials Engineering, National Central University, No. 300, Jhongda RD., Jhongli, Taoyuan, 32001, Taiwan. .,R & D Center for Membrane Technology, Chung Yuan Christian University, 200 Chung-Bei Rd., Jhongli, Taoyuan 320, Taiwan
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Khaing ZZ, Chen JY, Safarians G, Ezubeik S, Pedroncelli N, Duquette RD, Prasse T, Seidlits SK. Clinical Trials Targeting Secondary Damage after Traumatic Spinal Cord Injury. Int J Mol Sci 2023; 24:3824. [PMID: 36835233 PMCID: PMC9960771 DOI: 10.3390/ijms24043824] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/06/2023] [Accepted: 02/09/2023] [Indexed: 02/17/2023] Open
Abstract
Spinal cord injury (SCI) often causes loss of sensory and motor function resulting in a significant reduction in quality of life for patients. Currently, no therapies are available that can repair spinal cord tissue. After the primary SCI, an acute inflammatory response induces further tissue damage in a process known as secondary injury. Targeting secondary injury to prevent additional tissue damage during the acute and subacute phases of SCI represents a promising strategy to improve patient outcomes. Here, we review clinical trials of neuroprotective therapeutics expected to mitigate secondary injury, focusing primarily on those in the last decade. The strategies discussed are broadly categorized as acute-phase procedural/surgical interventions, systemically delivered pharmacological agents, and cell-based therapies. In addition, we summarize the potential for combinatorial therapies and considerations.
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Affiliation(s)
- Zin Z. Khaing
- Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA
| | - Jessica Y. Chen
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Gevick Safarians
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Sohib Ezubeik
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Nicolas Pedroncelli
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Rebecca D. Duquette
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA
- Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA
| | - Tobias Prasse
- Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA
- Department of Orthopedics and Trauma Surgery, University of Cologne, 50931 Cologne, Germany
| | - Stephanie K. Seidlits
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA
- Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA
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Milczarek O, Swadźba J, Swadźba P, Starowicz-Filip A, Krzyżewski RM, Kwiatkowski S, Majka M. Comparative Analysis of the Results of Stroke Treatment With Multiple Administrations of Wharton's Jelly Mesenchymal Stem Cells-Derived HE-ATMP and Standard Conservative Treatment: Case Series Study. Cell Transplant 2023; 32:9636897231195145. [PMID: 37644776 PMCID: PMC10469225 DOI: 10.1177/09636897231195145] [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: 11/28/2022] [Revised: 07/25/2023] [Accepted: 08/01/2023] [Indexed: 08/31/2023] Open
Abstract
Stroke remains still the leading cause of long-term disability worldwide. Although interventions such as early reperfusion, intravenous thrombolysis, and endovascular revascularization have shown neurological benefit in stroke patients, there is still lack of effective treatment enabling regeneration of nervous tissue after cerebral ischemic episodes. Cell therapy is an evolving opportunity for stroke survivors with residual neurological deficits. The purpose of this study was to evaluate safety and potential efficacy of multiple administration of Hospital Exemption-Advanced Therapy Medicinal Product (HE-ATMP) comprising 3 × 107 Wharton's jelly mesenchymal stem cells (WJMSCs). A study group was composed of six patients-three women and three men. The patients were qualified to the treatment with diagnosis of chronic stroke (2-24 months after cerebral ischemic episode), during 2 years. All the patients undergone repeated rounds of HE-ATMP administration to the CSF (cerebrospinal fluid) via lumbar puncture. The control group consisted of six patients (two women and four men) who experienced stroke, treated at the same time (follow-up period: 24 months) using standard treatment methods, without endovascular treatment. To evaluate the results of the therapy, we used both impairment scales [National Institutes of Health Stroke Score (NIHSS)] and functional outcomes scales [Modified Rankin Scale (MRS) and Barthel Index (BI)]. In four patients, who received at least three repeated rounds of HE-ATMP, we reported neurological improvement and reduction of functional neurodeficiency. The biggest improvement concerned the reduction of speech disorders in two cases; significant improvement in the field of motor skills in three patients and reduction of apraxia and improvement of logical communication skills in two patients were also reported. All the patients became more independent. Significant improvement of the neurological condition using the same scales was registered only in two patients from the control group. We did not report any adverse events in the treated group during follow-up. At 1-year follow-up, we demonstrate safety and beneficial effect of WJMSC transplantation including neurological improvement and reduction of functional neurodeficiency. We are aware that the samples size of this study is relatively small. The treatment regimen needs to be further tested in larger group of patients.
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Affiliation(s)
- Olga Milczarek
- Department of Children’s Neurosurgery, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Jakub Swadźba
- Department of Laboratory Medicine, Andrzej Frycz–Modrzewski Cracow University, Cracow, Poland
| | | | - Anna Starowicz-Filip
- Department of Psychology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Roger M. Krzyżewski
- Department of Neurosurgery and Neurotraumatology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Stanisław Kwiatkowski
- Department of Children’s Neurosurgery, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Marcin Majka
- Department of Transplantation, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
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Li X, Sun X, Wang B, Li Y, Tong J. Oncolytic virus-based hepatocellular carcinoma treatment: Current status, intravenous delivery strategies, and emerging combination therapeutic solutions. Asian J Pharm Sci 2023; 18:100771. [PMID: 36896445 PMCID: PMC9989663 DOI: 10.1016/j.ajps.2022.100771] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 10/24/2022] [Accepted: 12/04/2022] [Indexed: 12/30/2022] Open
Abstract
Current treatments for advanced hepatocellular carcinoma (HCC) have limited success in improving patients' quality of life and prolonging life expectancy. The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies. Recently, there has been increased interest in oncolytic viruses (OVs) as a therapeutic modality for HCC. OVs undergo selective replication in cancerous tissues and kill tumor cells. Strikingly, pexastimogene devacirepvec (Pexa-Vec) was granted an orphan drug status in HCC by the U.S. Food and Drug Administration (FDA) in 2013. Meanwhile, dozens of OVs are being tested in HCC-directed clinical and preclinical trials. In this review, the pathogenesis and current therapies of HCC are outlined. Next, we summarize multiple OVs as single therapeutic agents for the treatment of HCC, which have demonstrated certain efficacy and low toxicity. Emerging carrier cell-, bioengineered cell mimetic- or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described. In addition, we highlight the combination treatments between oncolytic virotherapy and other modalities. Finally, the clinical challenges and prospects of OV-based biotherapy are discussed, with the aim of continuing to develop a fascinating approach in HCC patients.
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Affiliation(s)
- Xinguo Li
- The First Hospital of China Medical University, Shenyang 110001, China
| | - Xiaonan Sun
- The 4th People's Hospital of Shenyang, Shenyang 110031, China
| | - Bingyuan Wang
- The First Hospital of China Medical University, Shenyang 110001, China
| | - Yiling Li
- The First Hospital of China Medical University, Shenyang 110001, China
| | - Jing Tong
- The First Hospital of China Medical University, Shenyang 110001, China
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Azarbarz N, Khorsandi L, Nejaddehbashi F, Neisi N, Nejad DB. Decellularized Wharton’s jelly scaffold enhances differentiation of mesenchymal stem cells to insulin-secreting cells. Tissue Cell 2022; 79:101938. [DOI: 10.1016/j.tice.2022.101938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 09/14/2022] [Accepted: 09/15/2022] [Indexed: 10/14/2022]
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Milczarek O, Kwiatkowski S, Swadźba J, Swadźba P, Kwiatkowska K, Majka M. Use of Multiple Wharton Jelly Mesenchymal Stem Cell Transplants in Treatment of Incomplete Spinal Cord Injury: A Case Report. EXP CLIN TRANSPLANT 2022; 20:878-882. [DOI: 10.6002/ect.2021.0283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Cheng YH, Chen KH, Sung YT, Yang CC, Chien CT. Intrarenal Arterial Transplantation of Dexmedetomidine Preconditioning Adipose Stem-Cell-Derived Microvesicles Confers Further Therapeutic Potential to Attenuate Renal Ischemia/Reperfusion Injury through miR-122-5p/Erythropoietin/Apoptosis Axis. Antioxidants (Basel) 2022; 11:1702. [PMID: 36139786 PMCID: PMC9495781 DOI: 10.3390/antiox11091702] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/19/2022] [Accepted: 08/29/2022] [Indexed: 11/19/2022] Open
Abstract
Intravenous adipose mesenchymal stem cells (ADSCs) attenuate renal ischemia/reperfusion (IR) injury but with major drawbacks, including the lack of a specific homing effect after systemic infusion, cell trapping in the lung, and early cell death in the damaged microenvironment. We examined whether intrarenal arterial transplantation of dexmedetomidine (DEX) preconditioning ADSC-derived microvesicles (DEX-MVs) could promote further therapeutic potential to reduce renal IR injury. We evaluated the effect of DEX-MVs on NRK-52E cells migration, hypoxia/reoxygenation (H/R)-induced cell death, and reactive oxygen species (ROS) amount and renal IR model in rats. IR was established by bilateral 45 min ischemia followed by 4 h reperfusion. Intrarenal MVs or DEX-MVs were administered prior to ischemia. Renal oxidative stress, hemodynamics and function, western blot, immunohistochemistry, and tubular injury scores were determined. The miR-122-5p expression in kidneys was analyzed using microarrays and quantitative RT-PCR and its action target was predicted by TargetScan. DEX-MVs were more efficient than MVs to increase migration capability and to further decrease H/R-induced cell death and ROS level in NRK-52E cells. Consistently, DEX-MVs were better than MV in increasing CD44 expression, improving IR-depressed renal hemodynamics and renal erythropoietin expression, inhibiting IR-enhanced renal ROS level, tubular injury score, miR-122-5p expression, pNF-κB expression, Bax/caspase 3/poly(ADP-ribose) polymerase (PARP)-mediated apoptosis, blood urea nitrogen, and creatinine levels. The use of NRK-52E cells confirmed that miR-122-5p mimic via inhibiting erythropoietin expression exacerbated Bax-mediated apoptosis, whereas miR-122-5p inhibitor via upregulating erythropoietin and Bcl-2 expression reduced apoptosis. In summary, intrarenal arterial DEX-MV conferred further therapeutic potential to reduce renal IR injury through the miR-122-5p/erythropoietin/apoptosis axis.
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Affiliation(s)
- Yu-Hsuan Cheng
- Department of Life Science, School of Life Science, College of Science, National Taiwan Normal University, No. 88, Section 4, Tingzhou Road, Taipei 11677, Taiwan; (Y.-H.C.); (Y.-T.S.)
| | - Kuo-Hsin Chen
- Department of Surgery, Division of General Surgery, Far-Eastern Memorial Hospital, New Taipei City 22056, Taiwan;
- Department of Electrical Engineering, Yuan Ze University, Taoyuan City 32003, Taiwan
| | - Yi-Ting Sung
- Department of Life Science, School of Life Science, College of Science, National Taiwan Normal University, No. 88, Section 4, Tingzhou Road, Taipei 11677, Taiwan; (Y.-H.C.); (Y.-T.S.)
| | - Chih-Ching Yang
- Department of Life Science, School of Life Science, College of Science, National Taiwan Normal University, No. 88, Section 4, Tingzhou Road, Taipei 11677, Taiwan; (Y.-H.C.); (Y.-T.S.)
- Office of Public Relation of Ministry of Health and Welfare, No. 488, Section 6, Zhongxiao E. Rd., Nangang District, Taipei 115204, Taiwan
- MacKay Junior College of Medicine, Nursing and Management, New Taipei City 11260, Taiwan
| | - Chiang-Ting Chien
- Department of Life Science, School of Life Science, College of Science, National Taiwan Normal University, No. 88, Section 4, Tingzhou Road, Taipei 11677, Taiwan; (Y.-H.C.); (Y.-T.S.)
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Barakat M, Hussein AM, Salama MF, Awadalla A, Barakat N, Serria M, El-Shafey M, El-Sherbiny M, El Adl MA. Possible Underlying Mechanisms for the Renoprotective Effect of Retinoic Acid-Pretreated Wharton's Jelly Mesenchymal Stem Cells against Renal Ischemia/Reperfusion Injury. Cells 2022; 11:1997. [PMID: 35805083 PMCID: PMC9266019 DOI: 10.3390/cells11131997] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 06/18/2022] [Accepted: 06/20/2022] [Indexed: 11/18/2022] Open
Abstract
Objectives: The current work investigated the effect of Wharton jelly mesenchymal stem cells (WJ-MSCs) pretreated with all-trans-retinoic acid (ATRA) on renal ischemia in rats and the possible role of oxidative stress, apoptotic and Wnt/β-Catenin signaling pathways, and inflammatory cytokines in their effects. Methods: The study included 90 male Sprague Dawley rats that were allocated to five groups (n = 18 rats): (I) Sham-operated group (right nephrectomy was performed); (II) Ischemia/reperfusion injury (IRI) group, a sham group with 45-min renal ischemia on the left kidney; (III) ATRA group, an ischemic group with an intravenous (i.v.) administration of ATRA 10 µM, 10 min post-surgery); (IV) WJ-MSCs group, an IRI group with an i.v. administration of 150 µL containing 7 × 106 WJ-MSCs, 10 min post-surgery; (V) WJ-MSCs + ATRA group, an IRI group with an i.v. administration of 150 µL of 7 × 106 WJ-MSCs pretreated with 10 µM ATRA. At the end of the experiments, serum creatinine, BUN micro-albuminuria (MAU), urinary protein, markers of redox state in the left kidney (MDA, CAT, SOD, and GSH), and the expression of Bax, IL-6, HIF-1α, Wnt7B, and β-catenin genes at the level of mRNA as well as for immunohistochemistry for NFkB and β-Catenin markers were analyzed. Results: The current study found that 45-min of renal ischemia resulted in significant impairment of kidney function (evidenced by the increase in serum creatinine, BUN, and urinary proteins) and deterioration of the kidney morphology, which was associated with a significant increase in redox state (evidenced by an increase in MDA and a decrease in GSH, SOD, and CAT), and a significant increase in inflammatory and apoptotic processes (evidenced by an increase in Bax and IL-6, NFkB, Wnt7B, β-catenin and HIF-1α) in kidney tissues (p < 0.05). On the other hand, treatment with ATRA, WJ-MSCs, or a combination of both, caused significant improvement in kidney function and morphology, which was associated with significant attenuation of oxidative stress, apoptotic markers, and inflammatory cytokines (IL6 and NFkB) with the upregulation of HIF-1α and β-catenin in kidney tissues (p < 0.05). Moreover, the renoprotective effect of WJ-MSCs pretreated with ATRA was more potent than WJ-MSCs alone. Conclusions: It is concluded that preconditioning of WJ-MSCs with ATRA may enhance their renoprotective effect. This effect could be due to the upregulation of the beta-catenin/Wnt pathway and attenuation of apoptosis, inflammation, and oxidative stress.
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Affiliation(s)
- Mai Barakat
- Department of Biochemistry, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt; (M.B.); (M.F.S.); (M.A.E.A.)
- Institute of Global Public Health and Human Ecology, School of Science and Engineering, American University, Cairo 11835, Egypt
| | - Abdelaziz M. Hussein
- Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Mohamed F. Salama
- Department of Biochemistry, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt; (M.B.); (M.F.S.); (M.A.E.A.)
| | - Amira Awadalla
- Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt; (A.A.); (N.B.)
| | - Nashwa Barakat
- Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt; (A.A.); (N.B.)
| | - Mohamed Serria
- Department of Biochemistry, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt;
| | - Mohamed El-Shafey
- Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt;
- Physiological Sciences Department, Fakeeh College for Medical Sciences, Jeddah 21461, Saudi Arabia
| | - Mohamed El-Sherbiny
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh 71666, Saudi Arabia;
| | - Mohamed A. El Adl
- Department of Biochemistry, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt; (M.B.); (M.F.S.); (M.A.E.A.)
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Comparison Study on the Effect of Mesenchymal Stem Cells-Conditioned Medium Derived from Adipose and Wharton’s Jelly on Versican Gene Expression in Hypoxia. IRANIAN BIOMEDICAL JOURNAL 2022; 26:202-8. [PMID: 35598150 PMCID: PMC9440690 DOI: 10.52547/ibj.26.3.202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Background: Mesenchymal stem cells enhance tissue repair through paracrine effects following transplantation. The versican protein is one of the important factors contributing to this repair mechanism. Using MSC conditioned medium for cultivating monocytes may increase versican protein production and could be a good alternative for transplantation of MSCs. This study investigates the effect of culture medium conditioned by human MSCs on the expression of the versican gene in PBMCs under hypoxia-mimetic and normoxic conditions. Methods: The conditioned media used were derived from either adipose tissue or from WJ. Flow cytometry for surface markers (CD105, CD73, and CD90) was used to confirm MSCs. The PBMCs were isolated and cultured with the culture media of the MSC derived from either the adipose tissue or WJ. Desferrioxamine and cobalt chloride (200 and 300 µM final concentrations, respectively) were added to monocytes media to induce hypoxia-mimetic conditions. Western blotting was applied to detect HIF-1α protein and confirm hypoxia-mimetic conditions in PBMC. Versican gene expression was assessed in PBMC using RT-PCR. Western blotting showed that the expression of HIF-1α in PBMC increased significantly (p < 0.01). Results: RT-PCR results demonstrated that the expression of the versican and VEGF genes in PBMC increased significantly (p < 0.01) in hypoxia-mimetic conditions as compared to normoxia. Conclusion: Based on the findings in the present study, the secreted factors of MSCs can be replaced by direct use of MSCs to improve damaged tissues.
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Wharton’s Jelly-Derived Mesenchymal Stem Cells with High Aurora Kinase A Expression Show Improved Proliferation, Migration, and Therapeutic Potential. Stem Cells Int 2022; 2022:4711499. [PMID: 35450345 PMCID: PMC9017458 DOI: 10.1155/2022/4711499] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 03/11/2022] [Indexed: 11/25/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are effective therapeutic agents that contribute to tissue repair and regeneration by secreting various factors. However, donor-dependent variations in MSC proliferation and therapeutic potentials result in variable production yields and clinical outcomes, thereby impeding MSC-based therapies. Hence, selection of MSCs with high proliferation and therapeutic potentials would be important for effective clinical application of MSCs. This study is aimed at identifying the upregulated genes in human Wharton's jelly-derived MSCs (WJ-MSCs) with high proliferation potential using mRNA sequencing. Aurora kinase A (AURKA) and dedicator of cytokinesis 2 (DOCK2) were selected as the upregulated genes, and their effects on proliferation, migration, and colony formation of the WJ-MSCs were verified using small interfering RNA (siRNA) techniques. mRNA expression levels of both the genes were positively correlated with the proliferation capacity of WJ-MSCs. Moreover, AURKA from human WJ-MSCs regulated the antiapoptotic effect of skeletal muscle cells by upregulating the chemokine (C motif) ligand (XCL1); this was further confirmed in the mdx mouse model. Taken together, the results indicated that AURKA and DOCK2 can be used as potential biomarkers for proliferation and migration of human WJ-MSCs. In particular, human WJ-MSCs with high expression of AURKA might have therapeutic efficacy against muscle diseases, such as Duchenne muscular dystrophy (DMD).
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Bates NM, Fallon ME, Hinds MT. In Vivo Imaging of Tissue-Engineered Grafts Within Pulmonary Artery of a Growing Large Animal Model. JACC Basic Transl Sci 2022; 7:220-222. [PMID: 35411317 PMCID: PMC8993903 DOI: 10.1016/j.jacbts.2022.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Affiliation(s)
- Novella M. Bates
- Biomedical Engineering Department, Oregon Health & Science University, Portland Oregon, USA
| | - Meghan E. Fallon
- Biomedical Engineering Department, Oregon Health & Science University, Portland Oregon, USA
| | - Monica T. Hinds
- Biomedical Engineering Department, Oregon Health & Science University, Portland Oregon, USA
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Rapetto F, Iacobazzi D, Narayan SA, Skeffington K, Salih T, Mostafa S, Alvino VV, Upex A, Madeddu P, Ghorbel MT, Caputo M. Wharton's Jelly-Mesenchymal Stem Cell-Engineered Conduit for Pulmonary Artery Reconstruction in Growing Piglets. JACC Basic Transl Sci 2022; 7:207-219. [PMID: 35411313 PMCID: PMC8993765 DOI: 10.1016/j.jacbts.2021.11.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 11/19/2021] [Accepted: 11/20/2021] [Indexed: 11/23/2022]
Abstract
Surgical treatment of congenital heart defects affecting the right ventricular outflow tract often requires complex reconstruction and multiple reoperations. With a randomized controlled trial, we compared a novel tissue-engineered small intestine submucosa-based graft for pulmonary artery reconstruction (seeded with mesenchymal stem cells derived from Wharton's Jelly) with conventional small intestine submucosa in growing piglets. Six months after implantation, seeded grafts showed integration with host tissues at cellular level and exhibited growth potential on transthoracic echocardiography and cardiovascular magnetic resonance. Our seeded graft is a promising biomaterial for pulmonary artery reconstruction in pediatric patients with right ventricular outflow tract abnormalities.
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Affiliation(s)
- Filippo Rapetto
- Department of Cardiac Surgery, Bristol Royal Hospital for Children, Bristol, United Kingdom
- Translational Health Sciences, University of Bristol, Bristol, United Kingdom
| | - Dominga Iacobazzi
- Translational Health Sciences, University of Bristol, Bristol, United Kingdom
| | - Srinivas A. Narayan
- Department of Paediatric Cardiology, Bristol Royal Hospital for Children, Bristol, United Kingdom
| | - Katie Skeffington
- Translational Health Sciences, University of Bristol, Bristol, United Kingdom
| | - Tasneem Salih
- Translational Health Sciences, University of Bristol, Bristol, United Kingdom
| | - Shahd Mostafa
- Translational Health Sciences, University of Bristol, Bristol, United Kingdom
| | - Valeria V. Alvino
- Translational Health Sciences, University of Bristol, Bristol, United Kingdom
| | - Adrian Upex
- Department of Anaesthesia, Bristol Royal Hospital for Children, Bristol, United Kingdom
| | - Paolo Madeddu
- Translational Health Sciences, University of Bristol, Bristol, United Kingdom
| | - Mohamed T. Ghorbel
- Translational Health Sciences, University of Bristol, Bristol, United Kingdom
| | - Massimo Caputo
- Department of Cardiac Surgery, Bristol Royal Hospital for Children, Bristol, United Kingdom
- Translational Health Sciences, University of Bristol, Bristol, United Kingdom
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Kang J, Guo Y. Human Umbilical Cord Mesenchymal Stem Cells Derived Exosomes Promote Neurological Function Recovery in a Rat Spinal Cord Injury Model. Neurochem Res 2022; 47:1532-1540. [PMID: 35132478 DOI: 10.1007/s11064-022-03545-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 01/20/2022] [Accepted: 01/27/2022] [Indexed: 02/04/2023]
Abstract
Spinal cord injury (SCI) often leads to personal and social-economic consequences with limited therapeutic options. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSC) have been explored as a promising alternative to cell therapies. In the current study, we explored the mechanism of hUC-MSC derived exosome's ameliorative effect on the spinal cord injury by combining data from in vivo contusion SCI model and in vitro cell viability of PC12 cell line stimulated with lipopolysaccharide. Intravenous administration of hUC-MSC derived exosomes dramatically improved motor function of Sprague-Dawley rats after SCI, with reduced apoptosis demonstrated by increased expression of B-cell lymphoma 2 (BCL2), decreased BCL2 associated X, apoptosis regulator (Bax), and reduced cleaved caspase 9. Conversely, exosome treatment reduced the transcription levels of astrocytes marker GFAP and microglia marker IBA1, suggesting a reduced inflammatory state from SCI injury. Furthermore, exosome treatment in vitro increased the cell viability of PC12 cells. Exosome application activated the Wnt/β-Catenin signaling in the spinal cord. Our study demonstrated that hUC-MSC derived exosomes could improve motor function through anti-apoptosis and anti-inflammatory effects. BCL2/Bax and Wnt/β-catenin signaling pathways were involved in the SCI process and could potentially mediate the protective effect of hUC-MSC derived exosomes.
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Affiliation(s)
- Jian Kang
- Department of Neurology, Liaocheng People's Hospital, No. 67 Dongchang West Road, Liaocheng, 252000, Shandong, China
| | - Yan Guo
- Department of Neurology, Liaocheng People's Hospital, No. 67 Dongchang West Road, Liaocheng, 252000, Shandong, China.
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Characteristics of Pooled Wharton's Jelly Mesenchymal Stromal Cells (WJ-MSCs) and their Potential Role in Rheumatoid Arthritis Treatment. Stem Cell Rev Rep 2022; 18:1851-1864. [PMID: 35113368 DOI: 10.1007/s12015-022-10344-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2022] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Mesenchymal stromal cells (MSC) from Wharton's jelly of umbilical cord is primitive and serve as an inexhaustible source of stem cells with greater potential in clinics. The existence of heterogeneity among the donor MSCs makes it difficult to predict the properties and clinical outcome of WJ-MSCs. We developed a strategy to minimize the donor to donor heterogeneity and produce consistency in biological properties by pooling three individual donors WJ-MSCs. Further, evaluated the effectiveness of the pooled MSCs in regulating the disease severity of Rheumatoid arthritis (RA) in animal models. METHODS WJ-MSCs were isolated from umbilical cord obtained from different donors, characterised and pooled based on the gender of baby. The biological properties of the pooled WJ-MSCs were compared to the individual WJ-MSCs. Further, the pooled WJ-MSCs were analysed for their safety profile in both in vitro and in vivo settings. The efficiency of pooled WJ-MSCs in regulating RA pathogenesis was also analysed in mice models of Collagen induced arthritis (CIA). RESULTS We identified differences in proliferation capacity, pro inflammatory gene expression levels among individual WJ-MSCs isolated from different donors and the variation is also attributed to gender difference. WJ-MSCs pooled and cultured from different donor's exhibit all the MSC characteristics and exhibited superior immunosuppressive capabilities. In the in vivo toxicity study, pooled MSCs are found to be safe, and further in the RA preclinical studies, they were found to decrease the disease severity in these animals. CONCLUSIONS Pooled WJ-MSCs reduces heterogeneity of individual donors and have superior immunosuppressive property. It is also effective in reducing the disease severity in the experimental animal models of RA.
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Mesenchymal Stem Cells in the Treatment of Human Spinal Cord Injury: The Effect on Individual Values of pNF-H, GFAP, S100 Proteins and Selected Growth Factors, Cytokines and Chemokines. Curr Issues Mol Biol 2022; 44:578-596. [PMID: 35723326 PMCID: PMC8929137 DOI: 10.3390/cimb44020040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/20/2022] [Accepted: 01/21/2022] [Indexed: 11/21/2022] Open
Abstract
At present, there is no effective way to treat the consequences of spinal cord injury (SCI). SCI leads to the death of neural and glial cells and widespread neuroinflammation with persisting for several weeks after the injury. Mesenchymal stem cells (MSCs) therapy is one of the most promising approaches in the treatment of this injury. The aim of this study was to characterize the expression profile of multiple cytokines, chemokines, growth factors, and so-called neuromarkers in the serum of an SCI patient treated with autologous bone marrow-derived MSCs (BM-MSCs). SCI resulted in a significant increase in the levels of neuromarkers and proteins involved in the inflammatory process. BM-MSCs administration resulted in significant changes in the levels of neuromarkers (S100, GFAP, and pNF-H) as well as changes in the expression of proteins and growth factors involved in the inflammatory response following SCI in the serum of a patient with traumatic SCI. Our preliminary results encouraged that BM-MSCs with their neuroprotective and immunomodulatory effects could affect the repair process after injury.
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