Pub Date : 2025-05-29eCollection Date: 2025-01-01DOI: 10.46582/jsrm.2101004
Saeideh Edalati, Pouyan Asadi, Mehdi Sheikh Arabi, Safoura Khajeniazi
Background: Exosomes are small vesicles with intracellular origin which are released into the extracellular space. The properties of stem cell-derived exosomes are similar to their cellular origin and can be involved in repair the damaged tissues. This investigation aimed to evaluate the effect of exosomes derived from mesenchymal stem cells and cardiomyocytes on the repair of damaged cardiomyocyte in vitro.
Methods: In this study, first damaged cells were created by Isopreternol treatment of mesenchymal-derived cardiomyocytes, then cells were affected by exosomes extracted from MSCs and MSC derived cardiomyocyes. Finally, mRNA levels of cardiac differentiation and damage markers were measured by Real Time PCR at the time intervals.
Results: Our results showed the level of cardiac markers in damaged cardiomyocytes increased after treatment by cardiomyocytes derived exosomes compared to MSC derived exosomes. Reciprocally LDH a and b mRNA levels decrease in both conditions.
Conclusion: our findings revealed the exosomes extracted from cardiomyocytes were more effective in the repair of injured cells compared to the exosomes derived MSCs.
外泌体是细胞内起源的小囊泡,被释放到细胞外空间。干细胞来源的外泌体的特性与其细胞起源相似,可以参与损伤组织的修复。本研究旨在评估间充质干细胞和心肌细胞来源的外泌体在体外修复受损心肌细胞中的作用。方法:在本研究中,首先用异戊二醇处理间充质来源的心肌细胞,形成损伤细胞,然后用从间充质干细胞和间充质来源的心肌细胞中提取的外泌体影响细胞。最后,通过Real Time PCR检测各组心脏分化和损伤标志物的mRNA水平。结果:我们的研究结果显示,与MSC来源的外泌体相比,心肌细胞来源的外泌体治疗后受损心肌细胞中的心脏标志物水平升高。相反,LDH a和b mRNA水平在两种情况下均下降。结论:我们的研究结果表明,与外泌体衍生的间充质干细胞相比,从心肌细胞中提取的外泌体在修复损伤细胞方面更有效。
{"title":"Comparative study the effect of human bone marrow mesenchymal stem cells and cardiomyocytes derived exosomes on improvement of Isoproterenol induced ischemic damaged cardiomyocytes.","authors":"Saeideh Edalati, Pouyan Asadi, Mehdi Sheikh Arabi, Safoura Khajeniazi","doi":"10.46582/jsrm.2101004","DOIUrl":"10.46582/jsrm.2101004","url":null,"abstract":"<p><strong>Background: </strong>Exosomes are small vesicles with intracellular origin which are released into the extracellular space. The properties of stem cell-derived exosomes are similar to their cellular origin and can be involved in repair the damaged tissues. This investigation aimed to evaluate the effect of exosomes derived from mesenchymal stem cells and cardiomyocytes on the repair of damaged cardiomyocyte in vitro.</p><p><strong>Methods: </strong>In this study, first damaged cells were created by Isopreternol treatment of mesenchymal-derived cardiomyocytes, then cells were affected by exosomes extracted from MSCs and MSC derived cardiomyocyes. Finally, mRNA levels of cardiac differentiation and damage markers were measured by Real Time PCR at the time intervals.</p><p><strong>Results: </strong>Our results showed the level of cardiac markers in damaged cardiomyocytes increased after treatment by cardiomyocytes derived exosomes compared to MSC derived exosomes. Reciprocally LDH a and b mRNA levels decrease in both conditions.</p><p><strong>Conclusion: </strong>our findings revealed the exosomes extracted from cardiomyocytes were more effective in the repair of injured cells compared to the exosomes derived MSCs.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"21 1","pages":"19-24"},"PeriodicalIF":1.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-24eCollection Date: 2025-01-01DOI: 10.46582/jsrm.2101003
Jie Chen, Tao Lin, Yue Yuan, Peilin Wu, Shishi Dai, Huan Xu, Jingyi Zhang, Jing Ma
The significant immunomodulatory capacity of mesenchymal stem cells (MSCs) is increasingly being recognized, making them valuable for the treatment of autoimmune disorders. MSCs influence immune cell behavior during therapy through intercellular communication mediated by extracellular vesicles (EVs). Moreover, MSC-derived apoptotic vesicles (apoEVs) can also exert immunomodulatory functions. This study compared the effects of dental follicle stem cells (DFSCs) and smaller apoptotic vesicles (apoSEVs) derived from DFSCs on the proliferation of peripheral blood mononuclear cells (PBMC), as well as their impact on T cell subpopulations and inflammatory factor expression. The results showed that apoSEVs derived from DFSCs significantly enhanced PBMC proliferation, inhibited Th1, Th17, and Treg cell populations, and reduced IFN-γ and TNF-α expression levels. These findings demonstrate that apoSEVsapoSEVs from DFSCs can effectively regulate immune responses in a manner similar to that of DFSCs themselves.
{"title":"Comparative Analysis of the Immunomodulatory Functions of Dental Follicle Stem Cells and Their Apoptotic Vesicles.","authors":"Jie Chen, Tao Lin, Yue Yuan, Peilin Wu, Shishi Dai, Huan Xu, Jingyi Zhang, Jing Ma","doi":"10.46582/jsrm.2101003","DOIUrl":"10.46582/jsrm.2101003","url":null,"abstract":"<p><p>The significant immunomodulatory capacity of mesenchymal stem cells (MSCs) is increasingly being recognized, making them valuable for the treatment of autoimmune disorders. MSCs influence immune cell behavior during therapy through intercellular communication mediated by extracellular vesicles (EVs). Moreover, MSC-derived apoptotic vesicles (apoEVs) can also exert immunomodulatory functions. This study compared the effects of dental follicle stem cells (DFSCs) and smaller apoptotic vesicles (apoSEVs) derived from DFSCs on the proliferation of peripheral blood mononuclear cells (PBMC), as well as their impact on T cell subpopulations and inflammatory factor expression. The results showed that apoSEVs derived from DFSCs significantly enhanced PBMC proliferation, inhibited Th1, Th17, and Treg cell populations, and reduced IFN-γ and TNF-α expression levels. These findings demonstrate that apoSEVsapoSEVs from DFSCs can effectively regulate immune responses in a manner similar to that of DFSCs themselves.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"21 1","pages":"11-18"},"PeriodicalIF":1.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-28eCollection Date: 2025-01-01DOI: 10.46582/jsrm.2101002
Baglan Kemelbekov, Ainur Amanzholkyzy, Samat Saparbayev, Edgaras Stankevicius
The proposed topic is important because it helps find a lot of problems that happen when cardiovascular diseases are passed on along with fibrosis and the link between stem cells and myocardial regeneration. This study aims to investigate the effectiveness of autologous stem cells in the treatment of post-infarction myocardial changes. Statistical, bibliographic, and bibliosemantic research methods and scientific literature for the last 6 years were used to achieve the purpose. Cardiovascular diseases hold the highest prevalence and mortality rates, second only to the number of accidents. Today, there are many methods in the fight against coronary heart disease. However, drug therapy is the least effective, and instrumental methods are too invasive and entail several complications and side effects. Therefore, conducting detailed research on the impact of stem cells on the myocardium affected by infarction presents a challenge. Stem cell transplantation, which includes autologous bone marrow stem cells, typically leads to noticeable and significant changes in cardiac hemodynamic parameters and rheological properties. The development of autologous bone marrow stem cells during the angiogenesis process substantiates such metamorphoses. In addition, factors such as vascular endothelial growth factor and the whole list of coagulogram indicators may influence these changes. The practical significance of the raised subject is using stem cell therapy as an alternative, less invasive method in the fight against postinfarction myocardial changes.
{"title":"Application of autologous stem cells in the treatment of ischaemic cardiomyopathy with heart failure after myocardial infarction.","authors":"Baglan Kemelbekov, Ainur Amanzholkyzy, Samat Saparbayev, Edgaras Stankevicius","doi":"10.46582/jsrm.2101002","DOIUrl":"10.46582/jsrm.2101002","url":null,"abstract":"<p><p>The proposed topic is important because it helps find a lot of problems that happen when cardiovascular diseases are passed on along with fibrosis and the link between stem cells and myocardial regeneration. This study aims to investigate the effectiveness of autologous stem cells in the treatment of post-infarction myocardial changes. Statistical, bibliographic, and bibliosemantic research methods and scientific literature for the last 6 years were used to achieve the purpose. Cardiovascular diseases hold the highest prevalence and mortality rates, second only to the number of accidents. Today, there are many methods in the fight against coronary heart disease. However, drug therapy is the least effective, and instrumental methods are too invasive and entail several complications and side effects. Therefore, conducting detailed research on the impact of stem cells on the myocardium affected by infarction presents a challenge. Stem cell transplantation, which includes autologous bone marrow stem cells, typically leads to noticeable and significant changes in cardiac hemodynamic parameters and rheological properties. The development of autologous bone marrow stem cells during the angiogenesis process substantiates such metamorphoses. In addition, factors such as vascular endothelial growth factor and the whole list of coagulogram indicators may influence these changes. The practical significance of the raised subject is using stem cell therapy as an alternative, less invasive method in the fight against postinfarction myocardial changes.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"21 1","pages":"3-10"},"PeriodicalIF":1.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-31eCollection Date: 2024-01-01DOI: 10.46582/jsrm.2002004
{"title":"Critical criteria for improvising the efficacy of transplanted cells; Significance of route of administration and microenvironment at the target site.","authors":"","doi":"10.46582/jsrm.2002004","DOIUrl":"10.46582/jsrm.2002004","url":null,"abstract":"","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"20 2","pages":"24-25"},"PeriodicalIF":1.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-31eCollection Date: 2024-01-01DOI: 10.46582/jsrm.2002007
Sajjad Ahmad
{"title":"(PASRM)-2024: I. Stem cell therapies for the cornea.","authors":"Sajjad Ahmad","doi":"10.46582/jsrm.2002007","DOIUrl":"10.46582/jsrm.2002007","url":null,"abstract":"","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"20 2","pages":"53-55"},"PeriodicalIF":1.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20eCollection Date: 2024-01-01DOI: 10.46582/jsrm.2002006
Winawati Eka Putri, Meidyta Sinantryana Widyaswari, Cita Rosita Sigit Prakoeswa, David Sajid Muhammad, Deny Febriwijaya Romadhani, Nadia Nisaussholihah
Background: Ultraviolet (UV) exposure causes direct and indirect damages to skin structures. Human adipose stem cell-conditioned medium (hASC-CM) is a collection of several soluble factors, such as cytokines, chemokines, and Growth Factors (GF), secreted by almost all living cells in the extracellular space which support wound healing and skin rejuvenation. Objective: To determine the effects of human adipose stem cell-conditioned medium (hASC-CM) in photoaged skin and evaluate photoaging improvement after treatment. Methods: An experimental randomized controlled trial was performed, involving 64 photoaged subjects at the Dermato-Venereology Outpatient Clinic of Jemursari Islamic Hospital Surabaya from March to June 2022. The subjects were divided into the hASC-CM group and vehiculum (control) group. Patients' transepidermal water loss value, skin tone, and Glogau score in weeks 0, 4, and 8 were evaluated. The data were then analyzed using Mann-Whitney test (p<0.05). Results: All subjects had Glogau scale of III (89.6%) with mean ± SD (3.121 ± 0.329). hASC-CM group showed higher improvements in the pore, wrinkle, spot polarized, spot UV parameters and skin tone compared to vehiculum group(p<0.05). Conclusions: hASC-CM effectively improved all parameters observed. The limitation of this research was on the lack of long-term follow-up after treatment. This research had received an ethical permit from The Ethical Committee Board of Jemursari Islamic Hospital Surabaya under letter 006/KEPK-RSISJS/II/2022.
{"title":"The Effect of Human Adipose Stem Cell-Conditioned Medium (hASC-CM) in Photoaged Skin.","authors":"Winawati Eka Putri, Meidyta Sinantryana Widyaswari, Cita Rosita Sigit Prakoeswa, David Sajid Muhammad, Deny Febriwijaya Romadhani, Nadia Nisaussholihah","doi":"10.46582/jsrm.2002006","DOIUrl":"10.46582/jsrm.2002006","url":null,"abstract":"<p><p><b>Background:</b> Ultraviolet (UV) exposure causes direct and indirect damages to skin structures. Human adipose stem cell-conditioned medium (hASC-CM) is a collection of several soluble factors, such as cytokines, chemokines, and Growth Factors (GF), secreted by almost all living cells in the extracellular space which support wound healing and skin rejuvenation. <b>Objective:</b> To determine the effects of human adipose stem cell-conditioned medium (hASC-CM) in photoaged skin and evaluate photoaging improvement after treatment. <b>Methods:</b> An experimental randomized controlled trial was performed, involving 64 photoaged subjects at the Dermato-Venereology Outpatient Clinic of Jemursari Islamic Hospital Surabaya from March to June 2022. The subjects were divided into the hASC-CM group and vehiculum (control) group. Patients' transepidermal water loss value, skin tone, and Glogau score in weeks 0, 4, and 8 were evaluated. The data were then analyzed using Mann-Whitney test (p<0.05). <b>Results:</b> All subjects had Glogau scale of III (89.6%) with mean ± SD (3.121 ± 0.329). hASC-CM group showed higher improvements in the pore, wrinkle, spot polarized, spot UV parameters and skin tone compared to vehiculum group(p<0.05). <b>Conclusions:</b> hASC-CM effectively improved all parameters observed. The limitation of this research was on the lack of long-term follow-up after treatment. This research had received an ethical permit from The Ethical Committee Board of Jemursari Islamic Hospital Surabaya under letter 006/KEPK-RSISJS/II/2022.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"20 2","pages":"47-52"},"PeriodicalIF":1.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-13eCollection Date: 2024-01-01DOI: 10.46582/jsrm.2002005
Samar Abdelbaset, Mohamed Ahmed Mohamed Sob, Ghada Mutawa, Mai Alaa El-Dein, Amoura Mohamed Abou-El-Naga
Background: In recent years, bone marrow derived mesenchymal stem cells (BM-derived MSCs) have emerged as a powerful cell-based therapy for various diseases, including male infertility. Aim: Demonstrating the efficiency of BM-derived MSCs transplantation by different routes of injection to home and repair testis of busulfan-induced azoospermic rats. Material and methods: In the present study, rat BM-derived MSC was isolated and characterized for mesenchymal &hematopoietic markers using flow-cytometry. Induction of infertility was induced by two successive doses of 10 mg/kg of busulfan. Azoospermic rats were treated by BM-derived MSCs which were injected via various routes (IP, IV, and local in testis). After 60 days; sperm analyses were performed beside mainly Biochemical, histopathological, immunohistological, and ultrastructural investigations. Results: BM-derived MSCs were expressed by CD44+ve, CD105+ve, CD106+ve, CD73+ve, CD34-ve, and CD45-ve. Sperm analysis showed a substantial improvement in sperm morphology, motility, and count following treatment with BM-derived MSCs. Caspase-3 and PCNA immunoexp ression accompanied with the levels of FSH, LH, testosterone, SOD, GSH and MDA depicted a considerable restoration of healthy levels after BM-derived MSCs treatment. The seminiferous tubules showed healthy morphology and spermatozoa were detected in their lumen according to the histopathological and ultrastructural analysis of BM-derived MSCs treated rats. Interestingly, BM-derived MSCs intravenous injection revealed the most significant infertility repair outcomes (P<0.05). Conclusion: Transplanted BM-derived MSCs had the potential to home in rat azoospermic testes and restore spermatogenesis. Consequently, the distinctive characteristics of BM-derived MSCs, such as their ability to differentiate and home, make them a promising cell-based therapeutic option for male infertility.
{"title":"Therapeutic Potential of Different Injection Methods for Bone Marrow Mesenchymal Stem Cell Transplantation in Buslfan-Induced Male Rat Infertility.","authors":"Samar Abdelbaset, Mohamed Ahmed Mohamed Sob, Ghada Mutawa, Mai Alaa El-Dein, Amoura Mohamed Abou-El-Naga","doi":"10.46582/jsrm.2002005","DOIUrl":"10.46582/jsrm.2002005","url":null,"abstract":"<p><p><b>Background:</b> In recent years, bone marrow derived mesenchymal stem cells (BM-derived MSCs) have emerged as a powerful cell-based therapy for various diseases, including male infertility. <b>Aim:</b> Demonstrating the efficiency of BM-derived MSCs transplantation by different routes of injection to home and repair testis of busulfan-induced azoospermic rats. <b>Material and methods:</b> In the present study, rat BM-derived MSC was isolated and characterized for mesenchymal &hematopoietic markers using flow-cytometry. Induction of infertility was induced by two successive doses of 10 mg/kg of busulfan. Azoospermic rats were treated by BM-derived MSCs which were injected via various routes (IP, IV, and local in testis). After 60 days; sperm analyses were performed beside mainly Biochemical, histopathological, immunohistological, and ultrastructural investigations. <b>Results:</b> BM-derived MSCs were expressed by CD44+ve, CD105+ve, CD106+ve, CD73+ve, CD34-ve, and CD45-ve. Sperm analysis showed a substantial improvement in sperm morphology, motility, and count following treatment with BM-derived MSCs. Caspase-3 and PCNA immunoexp ression accompanied with the levels of FSH, LH, testosterone, SOD, GSH and MDA depicted a considerable restoration of healthy levels after BM-derived MSCs treatment. The seminiferous tubules showed healthy morphology and spermatozoa were detected in their lumen according to the histopathological and ultrastructural analysis of BM-derived MSCs treated rats. Interestingly, BM-derived MSCs intravenous injection revealed the most significant infertility repair outcomes (P<0.05). <b>Conclusion:</b> Transplanted BM-derived MSCs had the potential to home in rat azoospermic testes and restore spermatogenesis. Consequently, the distinctive characteristics of BM-derived MSCs, such as their ability to differentiate and home, make them a promising cell-based therapeutic option for male infertility.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"20 2","pages":"26-46"},"PeriodicalIF":1.1,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31eCollection Date: 2024-01-01DOI: 10.46582/jsrm.2003003
Leila Dehghani, Iman Owliaee, Fatemeh Sadeghian, Ali Shojaeian
Wound healing is a complicated process that involves many different types of cells and signaling pathways. Mesenchymal stromal cells (MSCs) have shown great potential as a treatment to improve wound healing because they can modulate inflammation, promote the growth of new blood vessels, and stimulate the regeneration of tissue. Recent evidence indicates MSCs-derived extracellular vesicles known as exosomes may mediate many of the therapeutic effects of MSCs on wound healing. Exosomes contain bioactive molecules such as proteins, lipids, and RNAs that can be transferred to recipient cells to modulate cellular responses. This article reviews current evidence on the mechanisms and therapeutic effects of human umbilical cord MSCs (hUCMSCs)-derived exosomes on wound healing. In vitro and animal studies demonstrate that hUCMSC-derived exosomes promote fibroblast proliferation/migration, angiogenesis, and re-epithelialization while reducing inflammation and scar formation. These effects are mediated by exosomal transfer of cytokines, growth factors, and regulatory microRNAs that modulate signaling pathways involved in wound healing. Challenges remain in exosome isolation methods, optimizing targeting/retention, and translation to human studies. Nevertheless, hUCMSCs-derived exosomes show promise as a novel cell-free therapeutic approach to accelerate wound closure and improve healing outcomes. Further research is warranted to fully characterize hUCMSCs-exosomal mechanisms and explore their clinical potential for wound management.
{"title":"The Therapeutic Potential of Human Umbilical Cord Mesenchymal Stromal Cells Derived Exosomes for Wound Healing: Harnessing Exosomes as a Cell-free Therapy.","authors":"Leila Dehghani, Iman Owliaee, Fatemeh Sadeghian, Ali Shojaeian","doi":"10.46582/jsrm.2003003","DOIUrl":"10.46582/jsrm.2003003","url":null,"abstract":"<p><p>Wound healing is a complicated process that involves many different types of cells and signaling pathways. Mesenchymal stromal cells (MSCs) have shown great potential as a treatment to improve wound healing because they can modulate inflammation, promote the growth of new blood vessels, and stimulate the regeneration of tissue. Recent evidence indicates MSCs-derived extracellular vesicles known as exosomes may mediate many of the therapeutic effects of MSCs on wound healing. Exosomes contain bioactive molecules such as proteins, lipids, and RNAs that can be transferred to recipient cells to modulate cellular responses. This article reviews current evidence on the mechanisms and therapeutic effects of human umbilical cord MSCs (hUCMSCs)-derived exosomes on wound healing. In vitro and animal studies demonstrate that hUCMSC-derived exosomes promote fibroblast proliferation/migration, angiogenesis, and re-epithelialization while reducing inflammation and scar formation. These effects are mediated by exosomal transfer of cytokines, growth factors, and regulatory microRNAs that modulate signaling pathways involved in wound healing. Challenges remain in exosome isolation methods, optimizing targeting/retention, and translation to human studies. Nevertheless, hUCMSCs-derived exosomes show promise as a novel cell-free therapeutic approach to accelerate wound closure and improve healing outcomes. Further research is warranted to fully characterize hUCMSCs-exosomal mechanisms and explore their clinical potential for wound management.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"20 1","pages":"14-23"},"PeriodicalIF":1.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteoarthritis (OA) is a degenerative disease that causes chronic pain and disability worldwide. This disease is mainly caused by IL-1β and TNF-α, which lead to cartilage degradation and inhibit the repair capacity of damaged cartilage. Recent studies have shown that amniotic fluid mesenchymal stem cells (AF-MSCs) secrete proteins that can effectively help in the treatment of cartilage damaged by OA. However, the underlying mechanism is still unclear. Therefore, the aim of this study was to investigate the effects and mechanisms behind the healing properties of the AF-MSC secretome (AFS-se) under OA conditions. This study involved growing chondrocyte progenitor cells (CPCs) and traumatized cartilage tissues in the presence of the cytokines IL-1β and TNF-α, which mimic OA conditions. AFS-se was then added to the culture medium to determine its effect on the CPCs and cartilage. Cell migration, endogenous cell outgrowth, the expression of chondrogenic and anabolic genes, and the mechanism of proteins in the NF-κB and MAPK signaling pathways were examined in this study. AFS-se inhibited the inflammatory effects of IL-1β and TNF-α by significantly reducing ERK phosphorylation in the MAPK signaling pathway and decreasing downstream proinflammatory COX2 products. The impaired CPCs recovered their ability to migrate, and endogenous CPCs in injured osteoarthritic cartilage were able to regrow in response to inflammatory stimuli. Additionally, the expression of anabolic genes such as Col I, Col II, and IGF1 was restored in defective CPCs. In conclusion, this study demonstrated that AFS-se has therapeutic effects on OA by inhibiting the inflammatory functions of IL-1β and TNF-α through protein phosphorylation in the MAPK pathway while also promoting the regenerative and self-repair functions of CPCs in traumatized cartilage.
骨关节炎(OA)是一种退行性疾病,在全球范围内造成慢性疼痛和残疾。这种疾病的主要病因是 IL-1β 和 TNF-α,它们会导致软骨退化,抑制受损软骨的修复能力。最近的研究表明,羊水间充质干细胞(AF-MSCs)分泌的蛋白质可有效帮助治疗因 OA 而受损的软骨。然而,其潜在机制仍不清楚。因此,本研究的目的是探究在OA条件下AF-间充质干细胞分泌组(AFS-se)的疗效及其背后的机制。这项研究涉及在模拟 OA 条件的细胞因子 IL-1β 和 TNF-α 存在下培养软骨祖细胞(CPCs)和创伤软骨组织。然后在培养基中加入 AFS-se,以确定其对 CPCs 和软骨的影响。本研究考察了细胞迁移、内源性细胞生长、软骨生成基因和合成代谢基因的表达,以及 NF-κB 和 MAPK 信号通路蛋白的机制。AFS-se通过显著降低MAPK信号通路中的ERK磷酸化和减少下游促炎COX2产物,抑制了IL-1β和TNF-α的炎症效应。受损的 CPCs 恢复了迁移能力,受伤骨关节炎软骨中的内源性 CPCs 能够在炎症刺激下重新生长。此外,有缺陷的 CPCs 还恢复了 Col I、Col II 和 IGF1 等合成代谢基因的表达。总之,本研究表明,AFS-se 可通过 MAPK 通路中的蛋白磷酸化抑制 IL-1β 和 TNF-α 的炎症功能,同时促进创伤软骨中 CPC 的再生和自我修复功能,从而对 OA 起到治疗作用。
{"title":"MSC secretome from amniotic fluid halts IL-1β and TNF-α inflammation via the ERK/MAPK pathway, promoting cartilage regeneration in OA in vitro.","authors":"Supatra Klaymook, Napatara Tirawanchai, Suparat Wichitwiengrat, Puttachart Chuaynarong, Sasiprapa Thongbopit, Keerati Chareancholvanich, Tatsanee Phermthai","doi":"10.46582/jsrm.2001002","DOIUrl":"10.46582/jsrm.2001002","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a degenerative disease that causes chronic pain and disability worldwide. This disease is mainly caused by IL-1β and TNF-α, which lead to cartilage degradation and inhibit the repair capacity of damaged cartilage. Recent studies have shown that amniotic fluid mesenchymal stem cells (AF-MSCs) secrete proteins that can effectively help in the treatment of cartilage damaged by OA. However, the underlying mechanism is still unclear. Therefore, the aim of this study was to investigate the effects and mechanisms behind the healing properties of the AF-MSC secretome (AFS-se) under OA conditions. This study involved growing chondrocyte progenitor cells (CPCs) and traumatized cartilage tissues in the presence of the cytokines IL-1β and TNF-α, which mimic OA conditions. AFS-se was then added to the culture medium to determine its effect on the CPCs and cartilage. Cell migration, endogenous cell outgrowth, the expression of chondrogenic and anabolic genes, and the mechanism of proteins in the NF-κB and MAPK signaling pathways were examined in this study. AFS-se inhibited the inflammatory effects of IL-1β and TNF-α by significantly reducing ERK phosphorylation in the MAPK signaling pathway and decreasing downstream proinflammatory COX2 products. The impaired CPCs recovered their ability to migrate, and endogenous CPCs in injured osteoarthritic cartilage were able to regrow in response to inflammatory stimuli. Additionally, the expression of anabolic genes such as <i>Col I</i>, <i>Col II</i>, and <i>IGF1</i> was restored in defective CPCs. In conclusion, this study demonstrated that AFS-se has therapeutic effects on OA by inhibiting the inflammatory functions of IL-1β and TNF-α through protein phosphorylation in the MAPK pathway while also promoting the regenerative and self-repair functions of CPCs in traumatized cartilage.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"20 1","pages":"3-13"},"PeriodicalIF":1.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}