: Mesenchymal stem cells (MSCs) are adult stem cells with immunoregulatory abilities and low immunogenicity, exhibiting powerful immunosuppressive effects in various inflammatory diseases and holding promise for therapeutic applications. However, the detailed underlying mechanisms remain unclear. Multiple studies suggest that the immunomodulatory function of MSCs is primarily based on the release of immunoregulatory factors through paracrine effects, contributing to their therapeutic outcomes. Other studies report that the immunosuppressive effects of MSCs are mainly achieved through apoptosis, mitochondrial transfer, and the newly proposed migrasomes, highlighting their potential clinical implications. We propose a novel hypothesis, suggesting that migrasomes released by MSCs play a pivotal role in their immunomodulatory ability, potentially offering new avenues for therapeutic interventions. This article primarily summarizes the possible mechanisms by which MSCs exert their immunomodulatory effects, focusing on MSC apoptosis, mitochondrial transfer, and migrasomes, with implications for developing novel therapeutic strategies.
{"title":"Deciphering the Immunomodulatory Pathways of Mesenchymal Stem Cells","authors":"Fulin Yuan, Qi Qi, Lei Wang, Jinhua Pan, Xiaoyu Shi, Yu Zhang","doi":"10.2174/011574888x320528240826054546","DOIUrl":"https://doi.org/10.2174/011574888x320528240826054546","url":null,"abstract":": Mesenchymal stem cells (MSCs) are adult stem cells with immunoregulatory abilities and low immunogenicity, exhibiting powerful immunosuppressive effects in various inflammatory diseases and holding promise for therapeutic applications. However, the detailed underlying mechanisms remain unclear. Multiple studies suggest that the immunomodulatory function of MSCs is primarily based on the release of immunoregulatory factors through paracrine effects, contributing to their therapeutic outcomes. Other studies report that the immunosuppressive effects of MSCs are mainly achieved through apoptosis, mitochondrial transfer, and the newly proposed migrasomes, highlighting their potential clinical implications. We propose a novel hypothesis, suggesting that migrasomes released by MSCs play a pivotal role in their immunomodulatory ability, potentially offering new avenues for therapeutic interventions. This article primarily summarizes the possible mechanisms by which MSCs exert their immunomodulatory effects, focusing on MSC apoptosis, mitochondrial transfer, and migrasomes, with implications for developing novel therapeutic strategies.","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"277 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-28DOI: 10.2174/011574888x294038240723104727
Xiayanran Wu, Xueman Zhou, Yufan Zhu, Zhenzhen Zhang, Yanhua Dong, Jun Wang, Jin Liu
Stem cells play an indispensable part in bone formation, homeostasis, and regeneration. The origin of skeletal stem cells (SSCs) in long bones has been extensively discussed, and the major cell population is considered to reside in the perivascular niche of the bone marrow. Cranial bones are distinct from long bones in both the origins of their cell lineage and the manner of osteogenesis. Recently, multiple tissue-resident craniofacial stem cell populations have been identified, among which cranial suture-derived stem cells, known as suture mesenchymal stem cells (SuSCs), exhibit unique biological characteristics. Whether SuSCs have potential therapeutic uses to repair cranial bone defects and alleviate congenital skeletal diseases, represented mainly by craniosynostosis, is a question of great research value. This review focuses on craniofacial stem cells, especially SuSCs, with the goal of summarizing the latest progress as well as giving insight into their regulatory molecular mechanisms and potential therapeutic targets.
{"title":"Insights into Suture Stem Cells: Distributions, Characteristics, and Applications","authors":"Xiayanran Wu, Xueman Zhou, Yufan Zhu, Zhenzhen Zhang, Yanhua Dong, Jun Wang, Jin Liu","doi":"10.2174/011574888x294038240723104727","DOIUrl":"https://doi.org/10.2174/011574888x294038240723104727","url":null,"abstract":"Stem cells play an indispensable part in bone formation, homeostasis, and regeneration. The origin of skeletal stem cells (SSCs) in long bones has been extensively discussed, and the major cell population is considered to reside in the perivascular niche of the bone marrow. Cranial bones are distinct from long bones in both the origins of their cell lineage and the manner of osteogenesis. Recently, multiple tissue-resident craniofacial stem cell populations have been identified, among which cranial suture-derived stem cells, known as suture mesenchymal stem cells (SuSCs), exhibit unique biological characteristics. Whether SuSCs have potential therapeutic uses to repair cranial bone defects and alleviate congenital skeletal diseases, represented mainly by craniosynostosis, is a question of great research value. This review focuses on craniofacial stem cells, especially SuSCs, with the goal of summarizing the latest progress as well as giving insight into their regulatory molecular mechanisms and potential therapeutic targets.","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"4 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-30DOI: 10.2174/011574888x289224240723042538
Yaojun Suo, Chunfang Wang
Background: Spinal Cord Injury (SCI) results in motor, sensory, and autonomic dysfunctions and causes social and economic problems. Surgery, medication, and stem cell transplantation are therapeutic strategies for SCI. The use of endogenous neural stem cells seems preferable due to their lower immune responses. miR-126 serves as a promising microRNA for reducing inflammation after SCI. It can promote angiogenesis and proliferation of neural stem cells Objectives: This study aimed to observe changes in miR-126 expression after SCI in an animal mice model. Methods: A total of 42 healthy adult FVB mice were divided equally into 7 groups (6 SCI model versus 1 control). At different periods following SCI establishment in the model groups, Basso Mouse Scale score (BMS), histopathological changes, and expression levels of miR-126 were evaluated in the model groups compared to the control one. Results:: The BMS score increased to a certain extent as the time after spinal cord injury progressed. HE and Nissl staining showed that the acute period (1-7 days) after spinal cord injury was characterized by neuronal loss, whereas the chronic phase (21st day) was characterized by scar and cavity formation. Compared with the control group, the model group exhibited decreased expression of miR-126 during the acute phase (days 1-7 post-SCI). However, its expression increased by 21th day after SCI. Conclusion: Overexpressed miR-126 can contribute to reduced SCI-related damages, which may result in the promotion of the growth and proliferation of neural stem cells as well as the repair of motor function.
{"title":"A Study on the Role of miR-126 in the Repair Process after Spinal Cord Injury","authors":"Yaojun Suo, Chunfang Wang","doi":"10.2174/011574888x289224240723042538","DOIUrl":"https://doi.org/10.2174/011574888x289224240723042538","url":null,"abstract":"Background: Spinal Cord Injury (SCI) results in motor, sensory, and autonomic dysfunctions and causes social and economic problems. Surgery, medication, and stem cell transplantation are therapeutic strategies for SCI. The use of endogenous neural stem cells seems preferable due to their lower immune responses. miR-126 serves as a promising microRNA for reducing inflammation after SCI. It can promote angiogenesis and proliferation of neural stem cells Objectives: This study aimed to observe changes in miR-126 expression after SCI in an animal mice model. Methods: A total of 42 healthy adult FVB mice were divided equally into 7 groups (6 SCI model versus 1 control). At different periods following SCI establishment in the model groups, Basso Mouse Scale score (BMS), histopathological changes, and expression levels of miR-126 were evaluated in the model groups compared to the control one. Results:: The BMS score increased to a certain extent as the time after spinal cord injury progressed. HE and Nissl staining showed that the acute period (1-7 days) after spinal cord injury was characterized by neuronal loss, whereas the chronic phase (21st day) was characterized by scar and cavity formation. Compared with the control group, the model group exhibited decreased expression of miR-126 during the acute phase (days 1-7 post-SCI). However, its expression increased by 21th day after SCI. Conclusion: Overexpressed miR-126 can contribute to reduced SCI-related damages, which may result in the promotion of the growth and proliferation of neural stem cells as well as the repair of motor function.","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"96 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Nucleus pulposus mesenchymal stem cells play a fatal role in intervertebral disc homeostasis. Magnesium is an essential bioactive element for the human body, regulating intracellular enzyme activity and promoting stem cell adhesion and differentiation. Objective: This study aimed to detect the effects of Mg2+ on nucleus pulposus mesenchymal stem cells and explore the mechanism by which magnesium ions promote the differentiation of nucleus pulposus mesenchymal stem cells. Methods: Nucleus pulposus mesenchymal stem cells digested from the caudal intervertebral disc of 3-month-old SD rats were interfered with using different concentrations of magnesium ions, and their levels of migration, adhesion, and differentiation were evaluated by biochemical and molecular indices. Results: Magnesium ion treatment significantly enhanced the migration and adhesion ability of NPMSCs. Meanwhile, magnesium ion treatment promoted NP differentiation of NPMSCs and the formation of nucleus pulposus precipitates. p-Smad2 immunofluorescence staining demonstrated that the nuclear translocation of p-Smad2 was significantly up-regulated after Mg2+ stimulation, while this effect was significantly attenuated by the addition of β1 blocker. In addition, protein quantification experiments demonstrated the same results. These results showed that 10mM magnesium can significantly promote the differentiation of NPMSCs, and its mechanism is related to the integrin receptor and TGF-β signaling pathway. Conclusion: Mg2+ at 10 mM significantly promoted migration and differentiation of NPMSCs by a mechanism related to the integrin-TGF signaling pathway.
{"title":"Magnesium Regulates the Migration and Differentiation of NPMSCs via the Integrin Signaling Pathway","authors":"Dong Yin, Chongquan Huang, Changxiang Liang, Jianxiong Zhuang, Haobin Chen, Yue He, Hui Yu, Jin Xiao, Yongxiong Huang, Jielong Zhou, Xiangting Chen","doi":"10.2174/011574888x304570240705094512","DOIUrl":"https://doi.org/10.2174/011574888x304570240705094512","url":null,"abstract":"Background: Nucleus pulposus mesenchymal stem cells play a fatal role in intervertebral disc homeostasis. Magnesium is an essential bioactive element for the human body, regulating intracellular enzyme activity and promoting stem cell adhesion and differentiation. Objective: This study aimed to detect the effects of Mg2+ on nucleus pulposus mesenchymal stem cells and explore the mechanism by which magnesium ions promote the differentiation of nucleus pulposus mesenchymal stem cells. Methods: Nucleus pulposus mesenchymal stem cells digested from the caudal intervertebral disc of 3-month-old SD rats were interfered with using different concentrations of magnesium ions, and their levels of migration, adhesion, and differentiation were evaluated by biochemical and molecular indices. Results: Magnesium ion treatment significantly enhanced the migration and adhesion ability of NPMSCs. Meanwhile, magnesium ion treatment promoted NP differentiation of NPMSCs and the formation of nucleus pulposus precipitates. p-Smad2 immunofluorescence staining demonstrated that the nuclear translocation of p-Smad2 was significantly up-regulated after Mg2+ stimulation, while this effect was significantly attenuated by the addition of β1 blocker. In addition, protein quantification experiments demonstrated the same results. These results showed that 10mM magnesium can significantly promote the differentiation of NPMSCs, and its mechanism is related to the integrin receptor and TGF-β signaling pathway. Conclusion: Mg2+ at 10 mM significantly promoted migration and differentiation of NPMSCs by a mechanism related to the integrin-TGF signaling pathway.","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"13 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Cartilage has intrinsically limited healing power, and regeneration of cartilage damages has remained a challenge. Secreted products of mesenchymal stem cells have shown a new therapeutic strategies for cartilage injuries. Also it has been observed that low frequency electromagnetic field plays a key role in biological processes. Objective: This research was performed to investigate the synergic effect of mesenchymal stem cell-derived exosomes and low frequency electromagnetic field on chondrogenic differentiation. Methods: In this in vitro study, mesenchymal stem cell-derived exosomes were identified using AFM, SEM, TEM microscopy, and DLS method. Cells were treated in chondrogenic medium by exosomes, low frequency electromagnetic field, and the synergy of both. The cell survival was examined using MTT and Annexin methods, and cartilage differentiation was confirmed by Alcian blue staining. The expression of Sox-9, Acan, Col 2a1 and Col 10a1 genes was examined via Real- Time PCR technique on day 14 post-treatment. Results: The results confirmed the presence of exosomes with an approximate size of less than 100 nm. The results of Alcian blue revealed greater expression of glycosaminoglycans in the synergic treatment group compared to the other groups. Real-time PCR showed a significant increase in the expression of Sox-9, Acan, and Col 2a1 genes, as well as a significant reduction of Col 10a1 gene expression in the synergic treatment group compared to other groups. Conclusion: This study indicated that the synergic effect of exosome and low-frequency electromagnetic fields would lead to enhanced chondrogenic differentiation, which can be further explored in future clinical studies
{"title":"Examining the Synergic Effect of Exosomes Derived from Mouse Mesenchymal Stem Cells and Low-frequency Electromagnetic Field on Chondrogenic Differentiation","authors":"Maryam Lotfi, Javad Baharara, Khadije Nejad Shahrokhabadi, Pejman Khorshid","doi":"10.2174/011574888x314834240628110545","DOIUrl":"https://doi.org/10.2174/011574888x314834240628110545","url":null,"abstract":"Background: Cartilage has intrinsically limited healing power, and regeneration of cartilage damages has remained a challenge. Secreted products of mesenchymal stem cells have shown a new therapeutic strategies for cartilage injuries. Also it has been observed that low frequency electromagnetic field plays a key role in biological processes. Objective: This research was performed to investigate the synergic effect of mesenchymal stem cell-derived exosomes and low frequency electromagnetic field on chondrogenic differentiation. Methods: In this in vitro study, mesenchymal stem cell-derived exosomes were identified using AFM, SEM, TEM microscopy, and DLS method. Cells were treated in chondrogenic medium by exosomes, low frequency electromagnetic field, and the synergy of both. The cell survival was examined using MTT and Annexin methods, and cartilage differentiation was confirmed by Alcian blue staining. The expression of Sox-9, Acan, Col 2a1 and Col 10a1 genes was examined via Real- Time PCR technique on day 14 post-treatment. Results: The results confirmed the presence of exosomes with an approximate size of less than 100 nm. The results of Alcian blue revealed greater expression of glycosaminoglycans in the synergic treatment group compared to the other groups. Real-time PCR showed a significant increase in the expression of Sox-9, Acan, and Col 2a1 genes, as well as a significant reduction of Col 10a1 gene expression in the synergic treatment group compared to other groups. Conclusion: This study indicated that the synergic effect of exosome and low-frequency electromagnetic fields would lead to enhanced chondrogenic differentiation, which can be further explored in future clinical studies","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"53 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141586347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.2174/011574888x304709240628092958
Zhao Gao, Ying Li, Yage Zhang, Liangliang Xu, Yuxin Sun
Background: Osteoporotic fracture is a pathological fracture secondary to osteoporosis, causing disabilities and a heavy burden to the patients. In the previous study, we found that salvianolic acid B (SalB) promoted the osteogenesis of Mesenchymal Stem Cells (MSCs). Objective: This study aimed to explore the role of SalB in osteoporotic fracture healing, as well as the potential molecular mechanism. Methods: Human bone marrow mesenchymal stem cells (hMSCs) were treated with SalB or PBS in vitro, and an osteoporotic fracture model in Sprague-Dawley (SD) rats was established successfully. SalB or PBS was locally injected at the fracture. Eight weeks later, microCT was used to compare the healing of osteoporotic fractures with or without SalB. The relative expressions of mRNAs were measured by qRT-PCR. Bioinformatics analysis, RT-PCR, and dual luciferase reporter assay were utilized to detect the interrelation of genes. Immunohistochemistry staining was used to test expressions of proteins. Results: In the present study, we found that SalB significantly increased the level of lncRNA-- MALAT1 in a dose-dependent manner. Additionally, silencing lncRNA-MALAT1 inhibited the expressions of osteogenesis-related marker genes and abolished the effect of SalB on osteogenesis. Also, we found that lncRNA-MALAT1 sponged miR-155-5p, and miR-155-5p directly targeted HIF-1α. Using the osteoporotic fracture healing model, our result demonstrated that local administration of SalB could promote both bone and type H vessel formation in the calluses. The mechanical test further showed that SalB could improve the mechanical properties of fractured femurs. Conclusion: Taken together, our study reported that SalB could promote osteogenesis and type H vessel formation to accelerate osteoporotic fracture healing through the lncRNA-- MALAT1/miR-155-5p/HIF-1α axis.
{"title":"Salvianolic Acid B Accelerates Osteoporotic Fracture Healing via LncRNA-MALAT1/miR-155-5p/HIF1A Axis","authors":"Zhao Gao, Ying Li, Yage Zhang, Liangliang Xu, Yuxin Sun","doi":"10.2174/011574888x304709240628092958","DOIUrl":"https://doi.org/10.2174/011574888x304709240628092958","url":null,"abstract":"Background: Osteoporotic fracture is a pathological fracture secondary to osteoporosis, causing disabilities and a heavy burden to the patients. In the previous study, we found that salvianolic acid B (SalB) promoted the osteogenesis of Mesenchymal Stem Cells (MSCs). Objective: This study aimed to explore the role of SalB in osteoporotic fracture healing, as well as the potential molecular mechanism. Methods: Human bone marrow mesenchymal stem cells (hMSCs) were treated with SalB or PBS in vitro, and an osteoporotic fracture model in Sprague-Dawley (SD) rats was established successfully. SalB or PBS was locally injected at the fracture. Eight weeks later, microCT was used to compare the healing of osteoporotic fractures with or without SalB. The relative expressions of mRNAs were measured by qRT-PCR. Bioinformatics analysis, RT-PCR, and dual luciferase reporter assay were utilized to detect the interrelation of genes. Immunohistochemistry staining was used to test expressions of proteins. Results: In the present study, we found that SalB significantly increased the level of lncRNA-- MALAT1 in a dose-dependent manner. Additionally, silencing lncRNA-MALAT1 inhibited the expressions of osteogenesis-related marker genes and abolished the effect of SalB on osteogenesis. Also, we found that lncRNA-MALAT1 sponged miR-155-5p, and miR-155-5p directly targeted HIF-1α. Using the osteoporotic fracture healing model, our result demonstrated that local administration of SalB could promote both bone and type H vessel formation in the calluses. The mechanical test further showed that SalB could improve the mechanical properties of fractured femurs. Conclusion: Taken together, our study reported that SalB could promote osteogenesis and type H vessel formation to accelerate osteoporotic fracture healing through the lncRNA-- MALAT1/miR-155-5p/HIF-1α axis.","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"23 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141586345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.2174/011574888x292446240626072758
Wenzhi Shu, Yisu Song, Zhengyang Lu Lu, Renyi Su, Mengfan Yang, Ze Xiang, Chenhao Xu, Shusen Zheng, Xiao Xu, Xuyong Wei
Background and Aim: Post-Hepatectomy Liver Failure (PHLF) leads to a poor prognosis in patients receiving hepatectomy treatment, and cell therapy can promote liver regeneration. In this study, we investigated the therapeutic potential of human Amniotic Epithelial Cells (hAECs) in promoting liver regeneration after partial hepatectomy (PHx) and the underlying molecular mechanism. Methods: We established a 70% PHx liver regeneration model, after which 5×105 hAECs were injected into the tail vein of mice. The resulting liver function, weight, and immunohistochemistry data were analyzed to determine whether hAECs can promote liver regeneration. Then, we explored the possible mechanism by which hAECs promote liver regeneration after PHx through RNA sequencing. Finally, western blotting and immunofluorescence were used to confirm the discovered potential mechanism and signaling pathway involved. Results: The mice in the hAECs group displayed enhanced liver regeneration 48 hours after 70% PHx and the expression levels of cell proliferation-related proteins were significantly higher than those in the control group. RNA sequencing analysis revealed that the key signaling pathway through which hAECs promote liver regeneration is the FOXO3a pathway. Mechanistically, IL-6 activates FOXO3a through STAT3, thereby promoting liver autophagy to enhance liver regeneration after PHx. Finally, western blotting and immunofluorescence confirmed that the IL-6/STAT3/ FOXO3a pathway promotes liver regeneration by activating autophagy. Conclusion: These results suggest that hAEC treatment promoted liver regeneration after PHx through the IL-6/ STAT3/FOXO3a/autophagy pathway.
{"title":"Human Amniotic Epithelial Stem Cells Activate Autophagy via the IL-6/STAT3/FOXO3a Pathway to Facilitate Liver Regeneration Following Hepatectomy","authors":"Wenzhi Shu, Yisu Song, Zhengyang Lu Lu, Renyi Su, Mengfan Yang, Ze Xiang, Chenhao Xu, Shusen Zheng, Xiao Xu, Xuyong Wei","doi":"10.2174/011574888x292446240626072758","DOIUrl":"https://doi.org/10.2174/011574888x292446240626072758","url":null,"abstract":"Background and Aim: Post-Hepatectomy Liver Failure (PHLF) leads to a poor prognosis in patients receiving hepatectomy treatment, and cell therapy can promote liver regeneration. In this study, we investigated the therapeutic potential of human Amniotic Epithelial Cells (hAECs) in promoting liver regeneration after partial hepatectomy (PHx) and the underlying molecular mechanism. Methods: We established a 70% PHx liver regeneration model, after which 5×105 hAECs were injected into the tail vein of mice. The resulting liver function, weight, and immunohistochemistry data were analyzed to determine whether hAECs can promote liver regeneration. Then, we explored the possible mechanism by which hAECs promote liver regeneration after PHx through RNA sequencing. Finally, western blotting and immunofluorescence were used to confirm the discovered potential mechanism and signaling pathway involved. Results: The mice in the hAECs group displayed enhanced liver regeneration 48 hours after 70% PHx and the expression levels of cell proliferation-related proteins were significantly higher than those in the control group. RNA sequencing analysis revealed that the key signaling pathway through which hAECs promote liver regeneration is the FOXO3a pathway. Mechanistically, IL-6 activates FOXO3a through STAT3, thereby promoting liver autophagy to enhance liver regeneration after PHx. Finally, western blotting and immunofluorescence confirmed that the IL-6/STAT3/ FOXO3a pathway promotes liver regeneration by activating autophagy. Conclusion: These results suggest that hAEC treatment promoted liver regeneration after PHx through the IL-6/ STAT3/FOXO3a/autophagy pathway.","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"90 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141570202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Hypoxia is a common hallmark in both physiological and pathological states. The adaptation to hypoxia is a key cellular event in the development and differentiation of stem cells, as well as in pathological conditions such as ischemia. The hypoxic microenvironment, culture conditions, and reactive oxygen species (ROS) scavengers have all been shown to enhance the proliferation, anti-aging properties, immunomodulatory capabilities, differentiation potential, and regenerative and therapeutic potential of dental pulp stem cells (DPSCs). However, severe and persistent hypoxia can be detrimental to the survival and tissue regeneration of DPSCs. Therefore, hypoxic preconditioning of DPSCs and applying oxygen-releasing materials to mitigate extreme hypoxia can enhance the regenerative and therapeutic potential in damaged organisms. This article provides a comprehensive review of the influence of the hypoxic microenvironment on the biological characteristics of dental pulp stem cells (DPSCs). It also presents a summary of the recent research advances in DPSCs regarding tissue regeneration, particularly focusing on the utilization of hypoxic preconditioning. Additionally, this review highlights the diverse biological effects of hypoxia on tissue regeneration and proposes promising novel therapeutic strategies.
{"title":"Hypoxia-driven Dental Pulp Stem Cells as a Promising Strategy for Tissue Regeneration","authors":"Chengcheng Liao, Lulu Chen, Mingli Xiang, Sichen Long, Meiling Xiang, Linlin Xiao, Qian Long, Jianguo Liu, Xiaoyan Guan","doi":"10.2174/011574888x312892240625091241","DOIUrl":"https://doi.org/10.2174/011574888x312892240625091241","url":null,"abstract":": Hypoxia is a common hallmark in both physiological and pathological states. The adaptation to hypoxia is a key cellular event in the development and differentiation of stem cells, as well as in pathological conditions such as ischemia. The hypoxic microenvironment, culture conditions, and reactive oxygen species (ROS) scavengers have all been shown to enhance the proliferation, anti-aging properties, immunomodulatory capabilities, differentiation potential, and regenerative and therapeutic potential of dental pulp stem cells (DPSCs). However, severe and persistent hypoxia can be detrimental to the survival and tissue regeneration of DPSCs. Therefore, hypoxic preconditioning of DPSCs and applying oxygen-releasing materials to mitigate extreme hypoxia can enhance the regenerative and therapeutic potential in damaged organisms. This article provides a comprehensive review of the influence of the hypoxic microenvironment on the biological characteristics of dental pulp stem cells (DPSCs). It also presents a summary of the recent research advances in DPSCs regarding tissue regeneration, particularly focusing on the utilization of hypoxic preconditioning. Additionally, this review highlights the diverse biological effects of hypoxia on tissue regeneration and proposes promising novel therapeutic strategies.","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141570203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28DOI: 10.2174/011574888x301827240613063513
Hong-Xu Chen, Hong-Jun Xu, Wang Zhang, Zi-Yu Luo, Zhong-Xia Zhang, Hao-Han Shi, Yu-Chang Dong, Zhan-Jun Xue, Ying Ben, Sheng-Jun An
Objective: Parkinson’s disease (PD) is a progressive neurodegenerative disorder with symptoms including tremor and bradykinesia, while traditional dopamine replacement therapy and hypothalamic deep brain stimulation can temporarily relieve patients’ symptoms, they cannot cure the disease. Hence, discovering new methods is crucial to designing more effective therapeutic approaches to address the condition. In our previous study, we found that exosomes (Exos) derived from human umbilical cord mesenchymal stem cells (hucMSCs) repaired a PD model by inducing dopaminergic neuron autophagy and inhibiting microglia. However, it is not clear whether its therapeutic effect is related to inhibiting apoptosis by inhibiting caspase-3 expression. Methods: Three intervention schemes were used concerning previous literature, and the dosage of each scheme is the same, with different dosing intervals and treatment courses and to compare the aspects of behavior, histomorphology, and biochemical indexes. To predict and determine target gene enrichment, high-throughput sequencing and miRNA expression profiling of exosomes, GO and KEGG analysis, and Western blot were used. Results: Exos labeled with PKH67 were found to reach the substantia nigra through the blood- -brain barrier and existed in the liver and spleen. 6-hydroxydopamine (6-OHDA) induced PD rats were treated with Exos every two days for one month, which alleviated the asymmetric rotation induced by morphine, reduced the loss of dopaminergic neurons in the substantia nigra, and increased dopamine levels in the striatum. The effect became more significant as the treatment time was extended to two months. These results suggest that hucMSCs-Exos can inhibit the 6-OHDA- induced neuron damage in PD rats, and its neuroprotective effects may be mediated by inhibiting cell apoptosis. Through high-throughput sequencing of miRNA, potential targets for Exos to inhibit apoptosis may be BAD, IKBKB, TRAF2, BCL2, and CYCS. Conclusion: The above results indicate that hucMSCs-Exos can inhibit 6-OHDA-induced damage in PD rats, and its neuroprotective effect may be mediated by inhibiting cell apoptosis.
{"title":"HucMSCs-derived Exosomes Protect Against 6-hydroxydopamine-induced Parkinson’s Disease in Rats by Inhibiting Caspase-3 Expression and Suppressing Apoptosis","authors":"Hong-Xu Chen, Hong-Jun Xu, Wang Zhang, Zi-Yu Luo, Zhong-Xia Zhang, Hao-Han Shi, Yu-Chang Dong, Zhan-Jun Xue, Ying Ben, Sheng-Jun An","doi":"10.2174/011574888x301827240613063513","DOIUrl":"https://doi.org/10.2174/011574888x301827240613063513","url":null,"abstract":"Objective: Parkinson’s disease (PD) is a progressive neurodegenerative disorder with symptoms including tremor and bradykinesia, while traditional dopamine replacement therapy and hypothalamic deep brain stimulation can temporarily relieve patients’ symptoms, they cannot cure the disease. Hence, discovering new methods is crucial to designing more effective therapeutic approaches to address the condition. In our previous study, we found that exosomes (Exos) derived from human umbilical cord mesenchymal stem cells (hucMSCs) repaired a PD model by inducing dopaminergic neuron autophagy and inhibiting microglia. However, it is not clear whether its therapeutic effect is related to inhibiting apoptosis by inhibiting caspase-3 expression. Methods: Three intervention schemes were used concerning previous literature, and the dosage of each scheme is the same, with different dosing intervals and treatment courses and to compare the aspects of behavior, histomorphology, and biochemical indexes. To predict and determine target gene enrichment, high-throughput sequencing and miRNA expression profiling of exosomes, GO and KEGG analysis, and Western blot were used. Results: Exos labeled with PKH67 were found to reach the substantia nigra through the blood- -brain barrier and existed in the liver and spleen. 6-hydroxydopamine (6-OHDA) induced PD rats were treated with Exos every two days for one month, which alleviated the asymmetric rotation induced by morphine, reduced the loss of dopaminergic neurons in the substantia nigra, and increased dopamine levels in the striatum. The effect became more significant as the treatment time was extended to two months. These results suggest that hucMSCs-Exos can inhibit the 6-OHDA- induced neuron damage in PD rats, and its neuroprotective effects may be mediated by inhibiting cell apoptosis. Through high-throughput sequencing of miRNA, potential targets for Exos to inhibit apoptosis may be BAD, IKBKB, TRAF2, BCL2, and CYCS. Conclusion: The above results indicate that hucMSCs-Exos can inhibit 6-OHDA-induced damage in PD rats, and its neuroprotective effect may be mediated by inhibiting cell apoptosis.","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"17 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141507660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Clinical application of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is a promising approach for the treatment of heart diseases. However, the tumorigenicity of hiPSC-CMs remains a concern for their clinical applications and the composition of the hiPSC-CM subtypes need to be clearly identified. Methods: In the present study, hiPSC-CMs were induced from hiPSCs via modulation of Wnt signaling followed by glucose deprivation purification. The structure, function, subpopulation composition, and tumorigenic risk of hiPSC-CMs were evaluated by single-cell RNA sequencing (scRNAseq), whole exome sequencing (WES), and integrated molecular biology, cell biology, electrophysiology, and/or animal experiments. Results: The high purity of hiPSC-CMs, determined by flow cytometry analysis, was generated. ScRNAseq analysis of differentiation day (D) 25 hiPSC-CMs did not identify the transcripts representative of undifferentiated hiPSCs. WES analysis showed a few newly acquired confidently identified mutations and no mutations in tumor susceptibility genes. Further, no tumor formation was observed after transplanting hiPSC-CMs into NOD-SCID mice for 3 months. Moreover, D25 hiPSC-CMs were composed of subtypes of ventricular-like cells (23.19%) and atrial-like cells (66.45%) in different cell cycle stages or mature levels, based on the scRNAseq analysis. Furthermore, a subpopulation of more mature ventricular cells (3.21%) was identified, which displayed significantly up-regulated signaling pathways related to myocardial contraction and action potentials. Additionally, a subpopulation of cardiomyocytes in an early differentiation stage (3.44%) experiencing nutrient stress-induced injury and heading toward apoptosis was observed. Conclusions: This study confirmed the biological safety of hiPSC-CMs and described the composition and expression profile of cardiac subtypes in hiPSC-CMs which provide standards for quality control and theoretical supports for the translational applications of hiPSC-CMs.
{"title":"The Low Tumorigenic Risk and Subtypes of Cardiomyocytes Derived from Human-induced Pluripotent Stem Cells","authors":"Jizhen Lu, Lu Zhang, Hongxia Cao, Xiaoxue Ma, Zhihui Bai, Hanyu Zhu, Yiyao Qi, Shoumei Zhang, Peng Zhang, Zhiying He, Huangtian Yang, Zhongmin Liu, Wenwen Jia","doi":"10.2174/011574888x318139240621051224","DOIUrl":"https://doi.org/10.2174/011574888x318139240621051224","url":null,"abstract":"Background: Clinical application of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is a promising approach for the treatment of heart diseases. However, the tumorigenicity of hiPSC-CMs remains a concern for their clinical applications and the composition of the hiPSC-CM subtypes need to be clearly identified. Methods: In the present study, hiPSC-CMs were induced from hiPSCs via modulation of Wnt signaling followed by glucose deprivation purification. The structure, function, subpopulation composition, and tumorigenic risk of hiPSC-CMs were evaluated by single-cell RNA sequencing (scRNAseq), whole exome sequencing (WES), and integrated molecular biology, cell biology, electrophysiology, and/or animal experiments. Results: The high purity of hiPSC-CMs, determined by flow cytometry analysis, was generated. ScRNAseq analysis of differentiation day (D) 25 hiPSC-CMs did not identify the transcripts representative of undifferentiated hiPSCs. WES analysis showed a few newly acquired confidently identified mutations and no mutations in tumor susceptibility genes. Further, no tumor formation was observed after transplanting hiPSC-CMs into NOD-SCID mice for 3 months. Moreover, D25 hiPSC-CMs were composed of subtypes of ventricular-like cells (23.19%) and atrial-like cells (66.45%) in different cell cycle stages or mature levels, based on the scRNAseq analysis. Furthermore, a subpopulation of more mature ventricular cells (3.21%) was identified, which displayed significantly up-regulated signaling pathways related to myocardial contraction and action potentials. Additionally, a subpopulation of cardiomyocytes in an early differentiation stage (3.44%) experiencing nutrient stress-induced injury and heading toward apoptosis was observed. Conclusions: This study confirmed the biological safety of hiPSC-CMs and described the composition and expression profile of cardiac subtypes in hiPSC-CMs which provide standards for quality control and theoretical supports for the translational applications of hiPSC-CMs.","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"20 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141507657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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