Qiaoling Wang, Xiaodong Su, Rongjia Zhu, Robert Chunhua Zhao
{"title":"cAMP Agonist Forskolin Disrupts Mitochondrial Metabolism and Induces Senescence in Human Mesenchymal Cells.","authors":"Qiaoling Wang, Xiaodong Su, Rongjia Zhu, Robert Chunhua Zhao","doi":"10.1089/scd.2022.0180","DOIUrl":"https://doi.org/10.1089/scd.2022.0180","url":null,"abstract":"<p><p>Adult-derived mesenchymal stem cells (MSCs) can be used in therapies for the treatment of various diseases. The MSCs derived from aging tissues or long-term MSC cultures could have diminished therapeutic effects compared with MSCs derived from younger tissues, but the underlying mechanism has not been completely established. Dysfunction of energy metabolism is one of the main mechanisms underlying cell senescence. Although cyclic adenosine monophosphate (cAMP) is known to inhibit cell division and proliferation in vitro, its impact on MSC senescence has not been described. In this study, we used forskolin, an adenylate cyclase agonist and cAMP inducer, to disrupt metabolism in human adipose-derived MSCs and investigate the effects of metabolic dysfunction on MSC senescence. Treatment of human MSCs with forskolin resulted in senescence phenotypes, including reduced proliferation, cell-cycle arrest, and enhanced expression of the cell aging markers p16 and p21. Further, the senescent MSCs exhibited increased adipogenesis capacity and decreased osteogenesis capacity as well as a senescence-associated secretory phenotype characterized by increased expression of several inflammatory factors. Forskolin-associated MSC senescence was mainly caused by oxidative stress-induced disruption of mitochondrial metabolism, and the senescent MSCs had high levels of reactive oxygen species and reduced sirtuin gene expression. Lastly, we found that cAMP inhibitor SQ22536 protects MSCs from forskolin-induced senescence and senescence-related inflammatory phenotype. Our results indicate that forskolin can cause senescence of human MSCs through oxidative stress-induced mitochondrial metabolic dysfunction, and thus the results provide a basis for developing strategies for improving the quality and efficacy of cultured MSCs for clinical use.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10697029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cyclosporin A Promotes Invasion and Migration of Extravillous Trophoblast Cells Derived from Human-Induced Pluripotent Stem Cells and Human Embryonic Stem Cells.","authors":"Jiaxing Wang, Ping Long, Shengnan Tian, Weihua Zu, Jing Liu, Bangyong Wu, Jilong Mao, Dan Li, Yanlin Ma, Yuanhua Huang","doi":"10.1089/scd.2022.0144","DOIUrl":"https://doi.org/10.1089/scd.2022.0144","url":null,"abstract":"<p><p>Extravillous trophoblast (EVT) cells play an essential role in the maternal-fetal interaction. Although abnormal development and function of EVT cells, including impaired migration and invasion capability, are believed to be etiologically linked to severe pregnancy disorders including pre-eclampsia, the associated molecular mechanisms are not clear due to the lack of an appropriate cell model in vitro. Cyclosporin A (CsA) is a macrolide immunosuppressant and also used in clinic to improve pregnancy outcomes. However, whether CsA has any effects on the function of EVT cells has not been well investigated. In this study, we induced differentiation of human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) into EVT cells (hiPSC-EVT and hESC-EVT cells, respectively) by Y27632, neuregulin-1 (NRG1), A83-01, and matrigel, and collected these derived EVT cells by flow cytometry for sorting cells positive for double human leukocyte antigen-G (HLA-G) and Cytokeratin7 (KRT7), both of which are EVT markers. We then investigated the effects of CsA on the invasion and migration of these derived EVT cells. We found that the hiPSC-EVT and hESC-EVT cells expressed high levels of the EVT markers such as KRT7, integrin alpha 5 (ITGA5), and HLA-G but low levels of OCT4, a stem cell marker, and that CsA significantly promoted the invasion and migration of hiPSC-EVT and hESC-EVT cells compared with HTR-8/SVneo cells. These results represent a possible cell model for studying the function of EVT cells and mechanism of pregnancy-related disorders associated with EVT. In addition, CsA may be used to treat pregnancy complications in clinic associated with deficient EVT function.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10758478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saeed S Alqahtani, Mark C Butcher, Gordon Ramage, Matthew J Dalby, William Mclean, Christopher J Nile
{"title":"Acetylcholine Receptors in Mesenchymal Stem Cells.","authors":"Saeed S Alqahtani, Mark C Butcher, Gordon Ramage, Matthew J Dalby, William Mclean, Christopher J Nile","doi":"10.1089/scd.2022.0201","DOIUrl":"https://doi.org/10.1089/scd.2022.0201","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are well known for their regenerative potential. Even though the ability of MSCs to proliferate and differentiate has been studied extensively, there remains much to learn about the signaling mechanisms and pathways that control proliferation and influence the differentiation phenotype. In recent years, there has been growing evidence for the utility of non-neuronal cholinergic signaling systems and that acetylcholine (ACh) plays an important ubiquitous role in cell-to-cell communication. Indeed, cholinergic signaling is hypothesized to occur in stem cells and ACh synthesis, as well as in ACh receptor (AChR) expression, has been identified in several stem cell populations, including MSCs. Furthermore, AChRs have been found to influence MSC regenerative potential. In humans, there are two major classes of AChRs, muscarinic AChRs and nicotinic AChRs, with each class possessing several subtypes or subunits. In this review, the expression and function of AChRs in different types of MSC are summarized with the aim of highlighting how AChRs play a pivotal role in regulating MSC regenerative function.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9268140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chen Chen, Xiaoming Hou, Fujia Jing, Tao Wang, Li Feng, James Kang
{"title":"Alteration of Transcriptomic Profile and Antiseptic Efficacy of Adipose-Derived Mesenchymal Stromal/Stem Cells Under Different Culture Conditions.","authors":"Chen Chen, Xiaoming Hou, Fujia Jing, Tao Wang, Li Feng, James Kang","doi":"10.1089/scd.2022.0238","DOIUrl":"https://doi.org/10.1089/scd.2022.0238","url":null,"abstract":"<p><p>Mesenchymal stromal/stem cells (MSCs) are a promising therapeutic agent for various diseases, including sepsis. However, translating MSC therapy to clinical applications remains challenging due to variations in the properties of MSCs under different preparation conditions. In this study, the gene expression profiles of human adipose-derived mesenchymal stromal/stem cells (ADSCs) under different culture conditions were compared in relation to their therapeutic efficacy for sepsis. Results showed that ADSCs cultured in media supplemented with human platelet lysates (hPL) (hPL-ADSCs) exhibited a smaller cell size and higher proliferative capacity, whereas ADSCs cultured in media supplemented with fetal bovine serum (FBS) (FBS-ADSCs) showed a broader and flatter shape. Both hPL-ADSCs and FBS-ADSCs exhibited a protective effect in a mouse model of sepsis; however, hPL-ADSCs displayed a better potency for immunosuppressive function, as evidenced by a better improvement of survival rate and further reduction of tissue injury and infectious biomarkers (alanine transaminase and procalcitonin). Furthermore, hPL-ADSCs caused a more anti-inflammatory transcriptomic shift, whereas FBS-ADSCs led to more depression of proinflammatory transcriptomic response. This study thus demonstrates that both hPL-ADSCs and FBS-ADSCs are effective for antiseptic therapy via different mechanisms of inflammatory manipulation, although hPL-ADSCs may imply a better preference.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9268676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Madhurima Das, Prajakta Teli, Anuradha Vaidya, Vaijayanti Prakash Kale
{"title":"Secretome of Young Mesenchymal Stromal Cells Rejuvenates Aged Mesenchymal Stromal Cells by Normalizing Their Phenotype and Restoring Their Differentiation Profile.","authors":"Madhurima Das, Prajakta Teli, Anuradha Vaidya, Vaijayanti Prakash Kale","doi":"10.1089/scd.2022.0213","DOIUrl":"https://doi.org/10.1089/scd.2022.0213","url":null,"abstract":"<p><p>During aging, the proliferation and differentiation ability of mesenchymal stem/stromal cells (MSCs) gets affected, and hence, aged MSCs are not preferred for regenerative purposes. Rapid identification of aging-associated changes within MSCs and the mechanistic pathways involved are necessary to determine optimal cell sources to treat musculoskeletal disorders in older patients. In the present study, we have identified a set of phenotypic markers, namely downregulated expression of CD90 and upregulated expression of CD45, as age-defining markers for the bone marrow-derived MSCs. We also show that these phenotypic changes in aged MSCs correlate with their aging-mediated differentiation defects. We find that oxidative stress signaling leading to the activation of nuclear factor kappa B (NF-κB) plays an essential role in altering the phenotype and differentiation ability of the aged MSCs. We further show that treatment of aged MSCs with the conditioned medium (CM) derived from young MSCs (young-CM) restored their phenotype and differentiation potential to the young-like by ameliorating activation of NF-κB signaling in them. Similar changes could also be achieved by using an inhibitor of NF-κB signaling, showing that oxidative stress-induced NF-κB activation is the causative factor in the aging of MSCs. Additionally, we show that treating young MSCs with hydrogen peroxide mimics all the aging-mediated changes in them, underscoring the involvement of oxidative stress in the aging of MSCs. Overall, our data suggest that the altered expression of CD90 and CD45 surface markers can be used as a primary screen to identify the onset of aging in the MSCs, which can be quickly reversed by their in vitro treatment with young-CM or NF-κB inhibitor. Our study also puts the phenotypic characterization of MSCs in a clinical perspective.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10690118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acknowledgment of Reviewers 2022.","authors":"","doi":"10.1089/scd.2022.29013.ack","DOIUrl":"https://doi.org/10.1089/scd.2022.29013.ack","url":null,"abstract":"","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10539418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Monocyte Chemoattractant Protein-1-Supplemented Plasma Enhances Adiponectin and Adipogenesis-Related Gene Expression.","authors":"Tzyy-Bin Tsay, Pei-Hsuan Chen, Merton Li, Chia-Hua Tang, Lee-Wei Chen","doi":"10.1089/scd.2022.0227","DOIUrl":"https://doi.org/10.1089/scd.2022.0227","url":null,"abstract":"<p><p>Increasing adipogenesis has been explored to treat metabolic diseases and atherosclerosis through the release of adiponectin. The effects and mechanism of platelet-rich plasma treatment on fat graft survival and adipogenesis have not been clarified. Here, we aimed to study the effects of monocyte chemoattractant protein-1 (MCP-1)-supplemented plasma on adipogenesis-related gene expression and adiponectin levels. Stromal vascular fractions (SVFs) purified from the inguinal adipose tissue of obese and diabetic (<i>Lepr<sup>db/db</sup></i>) mice were treated with plasma from control (<i>Lepr<sup>+/+</sup></i>) mice supplemented with 10 or 50 ng of MCP-1. The expression of adiponectin and interleukin-33 (IL-33) mRNA in adipose tissue was increased in <i>Lepr<sup>db/db</sup></i> mice, whereas control (<i>Lepr<sup>+/+</sup></i>) plasma reduced expression of IL-33 mRNA as well as peroxisome proliferator-activated receptor gamma (PPARγ), pJNK, and pNF-κB protein, and increased the expression of IL-10 mRNA in SVFs of <i>Lepr<sup>db/db</sup></i> mice. MCP-1-supplemented control plasma increased the expression of adiponectin, CCAAT-enhancer-binding protein α (C/EBPα), dipeptidyl peptidase 4 (DPP4), IL-33, and PDGFα mRNA and the expression of adiponectin protein as well as PPARγ of SVFs and the expression of PPARγ mRNA in adipose tissue macrophages (ATMs). Injection of MCP-1-supplemented plasma into adipose tissue of <i>Lepr<sup>db/db</sup></i> mice increased the expression of IL-33 and Col3a1 mRNA in SVFs and IL-33, FABP4, PDGFα, PPARγ and PPARγ2 of ATMs, protein expression of adiponectin and PPARγ of SVFs, and plasma adiponectin levels, as well as DPP4 activity. In conclusion, our results demonstrate that control plasma decreases adipogenesis and increases IL-10, and decreases IL-33, pJNK, and pNF-κB in adipose tissue. MCP-1-supplemented plasma enhances adipogenesis-related gene expression in SVFs and adiponectin levels, which may be mediated through an increase of IL-33 and PPARγ. Thus, our findings suggest that MCP-1-supplemented plasma represents a novel therapy to stimulate local adipogenesis and systemic adiponectin levels.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10700883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mesenchymal Stem Cells Promote Wound Healing and Effects on Expression of Matrix Metalloproteinases-8 and 9 in the Wound Tissue of Diabetic Rats.","authors":"Lingling Wei, Yongsong Xu, Lijie Zhang, Longyan Yang, Robert Chunhua Zhao, Dong Zhao","doi":"10.1089/scd.2021.0218","DOIUrl":"https://doi.org/10.1089/scd.2021.0218","url":null,"abstract":"<p><p>Diabetic foot ulcer (DFU) is a multifactorial complication of diabetes, mainly manifested as infection, ulcer, or destruction of deep tissue, and there is currently no effective treatment. Several preclinical and clinical studies have proved that the transplantation of mesenchymal stem cells (MSCs) improved wound healing. In this study, we evaluated the therapeutic efficacy of human umbilical cord (hUC-MSCs) in DFU rat model. One dose of hUC-MSCs (1 × 10<sup>6</sup> cells) was subcutaneously injected around wounds in male Sprague-Dawley rats. Wound healing was evaluated macroscopically (wound closure) every 3 days. In addition, we measured growth factors and specific proteins [matrix metalloproteinases (MMPs)-9 and MMP-8] on Day 14 post hUC-MSC transplantation. Results showed significant differences in the wound healing kinetics of lesions that received hUC-MSCs compared to lesions that received vehicle (phosphate buffered saline; <i>P</i> < 0.05). Enzyme-linked immunosorbent assay analyses indicated that MMP-9 protein contents were significantly upregulated in DFU animals, while MMP-8 was downregulated compared to the diabetic rats (<i>P</i> < 0.05). After MSC treatment, the level of MMP-9 and MMP-8 decreased and increased compared to the vehicle group, respectively. These findings suggest that hUC-MSC transplantation can ameliorate the healing process of DFU rats and a potential mechanism through which MSCs enhance DFU wound healing by decreasing MMP-9 expression and increasing MMP-8 expression. This study represents a promising opportunity to gain insight into how MSCs mediate wound healing.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10730572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yao Pan, Li Tang, Shuxian Dong, Mengjie Xu, Qiong Li, Guochen Zhu
{"title":"Exosomes from Hair Follicle Epidermal Neural Crest Stem Cells Promote Acellular Nerve Allografts to Bridge Rat Facial Nerve Defects.","authors":"Yao Pan, Li Tang, Shuxian Dong, Mengjie Xu, Qiong Li, Guochen Zhu","doi":"10.1089/scd.2022.0245","DOIUrl":"10.1089/scd.2022.0245","url":null,"abstract":"<p><p>Previous studies showed that acellular nerve allografts (ANAs) have been successfully utilized in repairing peripheral nerve defects, and exosomes produced by stem cells are useful in supporting axon regrowth after peripheral nerve injury. In this study, exosomes from hair follicle epidermal neural crest stem cells (EPI-NCSCs-Exos) combined with ANAs were used to bridge facial nerve defects. EPI-NCSCs-Exos were isolated by ultracentrifuge, and were identified. After coculture, EPI-NCSCs-Exos were internalized into dorsal root ganglions (DRGs) and schwann cells (SCs) in vitro, respectively. EPI-NCSCs-Exos elongate the length of axons and dendrites of DRGs, and accelerated the proliferation and migration of SCs, and increased neurotrophic factor expression of SCs as well. The next step was to assign 24 Sprague Dawley male rats randomly and equally into three groups: the autograft group, the ANA group, and the ANA + EPI-NCSCs-Exos group. Each rat manufactured a 5-mm gap of facial nerve defect and immediately bridged by the corresponding transplants, respectively. After surgery, behavioral changes and electrophysiological testing of each rat were observed and assessed. At 90 days postoperatively, the retrogradely fluorescent tracer-labeled neurons were successfully observed on the injured side in the three groups. Morphological changes of facial nerve regeneration were evaluated by transmission electron microscopy and semithin toluidine blue staining. The results showed that nerve fiber density, nerve fiber diameter, and myelin sheath thickness in the ANA group were significantly worse than those in the other two groups (<i>P</i> < 0.05). No significant difference in nerve fiber density and myelin sheath thickness was observed between the autograft group and the ANA + EPI-NCSCs-Exos group (<i>P</i> = 0.14; <i>P</i> = 0.23). Our data indicated that EPI-NCSCs-Exos facilitate ANAs to bridge facial nerve defects and have the potential to replace autograft therapy in clinic.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10701340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Bone Morphogenetic Protein Signaling Inhibitor, LDN193189, Converts Ischemia-Induced Multipotent Stem Cells into Neural Stem/Progenitor Cell-Like Cells.","authors":"Yusuke Minato, Akiko Nakano-Doi, Seishi Maeda, Takayuki Nakagomi, Hideshi Yagi","doi":"10.1089/scd.2022.0139","DOIUrl":"https://doi.org/10.1089/scd.2022.0139","url":null,"abstract":"<p><p>Stem cell therapy is used to restore neurological function in stroke patients. We have previously reported that ischemia-induced multipotent stem cells (iSCs), which are likely derived from brain pericytes, develop in poststroke human and mouse brains. Although we have demonstrated that iSCs can differentiate into neural lineage cells, the factors responsible for inducing this differentiation remain unclear. In this study, we found that LDN193189, a bone morphogenetic protein (BMP) inhibitor, caused irreversible changes in the shape of iSCs. In addition, compared with iSCs incubated without LDN193189, the iSCs incubated with LDN193189 (LDN-iSCs) showed upregulated expression of neural lineage-related genes and proteins, including those expressed in neural stem/progenitor cells (NSPCs), and downregulated expression of mesenchymal and pericytic-related genes and proteins. Moreover, microarray analysis revealed that LDN-iSCs and NSPCs had similar gene expression profiles. Furthermore, LDN-iSCs differentiated into electrophysiologically functional neurons. These results indicate that LDN193189 induces NSPC-like cells from iSCs, suggesting that bioactive molecules regulating BMP signaling are potential targets for promoting neurogenesis from iSCs in the pathological brain, such as during ischemic stroke. We believe that our findings will bring us one step closer to the clinical application of iSCs.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10384422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}