Stem Cell Research & Therapy最新文献

{"title":"Human dental follicle stem cell-derived exosomes reduce root resorption by inhibiting periodontal ligament cell pyroptosis.","authors":"Xinyi Li, Xinyang Liu, Jianing Zhou, Ping Zhang, Song Chen, Ding Bai","doi":"10.1186/s13287-025-04216-6","DOIUrl":"10.1186/s13287-025-04216-6","url":null,"abstract":"<p><strong>Background: </strong>To explore the therapeutic effects and mechanisms of the exosomes derived from dental follicle stem cells (DFSC-Exos) in reducing osteoclastogenesis and root resorption (RR) by inhibiting periodontal ligament cell (PDLC) pyroptosis.</p><p><strong>Methods: </strong>DFSC-Exos, with force stimulation (Force-Exos) or without (Ctrl-Exos), were co-cultured with human PDLCs in vitro and injected into the periodontal ligament (PDL) of rats following the establishment of RR models in vivo. Subsequently, resorption volume, PDLC pyroptotic ratio, and NLRP3-mediated pyroptosis pathway activation were performed to investigate the therapeutic effects of DFSC-Exos on PDLC pyroptosis during RR. Furthermore, the number of M1/M2 macrophages, osteoclast formation, and transwell polarization elucidated the role of Force-Exo treatment in macrophage polarization and osteoclastogenesis by inhibiting pyroptosis. Exosomal miRNA sequencing and bioinformatic analysis were used to identify differentially abundant exosome-derived miRNAs, as well as the dominant biological processes and pathways modulated by miRNA. The administration of miRNA inhibitors further verified the regulation of exosomal miRNA on RR via modulating pyroptosis. Moreover, the potential mechanisms involving candidate miRNAs and relevant pathways were explored.</p><p><strong>Results: </strong>Exosomes released by force-stimulated DFSCs (Force-Exos) inhibited NOD-like receptor 3 (NLRP3)-mediated PDLC pyroptosis, which impacted M1 macrophage activation and osteoclast formation. Based on exosomal miRNA sequencing, miR-140-3p in Force-Exos were transferred to PDLCs, and the administration of miR-140-3p inhibitors significantly reversed the reduction in PDLC pyroptosis, M1 macrophage polarization, osteoclast number, and resorption volume caused by Force-Exos. More importantly, mechanistic studies demonstrated that miR-140-3p mediated the function of Force-Exos by targeting DNA methyltransferase 1 (DNMT1) to alter the DNA methylation of suppressor of cytokine signaling (SOCS1) and the downstream nuclear factor κB (NF-κB) signaling pathway in PDLCs. Blocking the DNMT1/SOCS1/NFκB axis with DFSC-derived exosomal miR-140-3p downregulated NLRP3-mediated PDLC pyroptosis to impact M1 polarization and osteoclast formation, thereby alleviating RR.</p><p><strong>Conclusion: </strong>DFSC-Exos downregulated NLRP3-mediated PDLC pyroptosis via miR-140-3p to block DNMT1/SOCS1/NFκB axis, which impacted M1 polarization and osteoclast formation, thereby alleviating RR.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"79"},"PeriodicalIF":7.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional regeneration strategies of hair follicles: advances and challenges.","authors":"Xi Chu, Zhentao Zhou, Xifei Qian, Haiyan Shen, Hanxiao Cheng, Jufang Zhang","doi":"10.1186/s13287-025-04210-y","DOIUrl":"10.1186/s13287-025-04210-y","url":null,"abstract":"<p><p>Hair follicles are essential appendages of human skin that function in protection, sensation, thermoregulation and social interactions. The multicellular components, particularly the dermal papilla, matrix and bulge housing stem cells, enable cyclic hair growth postnatally. However, miniaturization and loss of hair follicles can occur in the context of ageing, trauma and various alopecia-related diseases. Conventional treatments involve the redistribution of existing follicles, which may not be viable in patients lacking follicular resources. Recent progress in the comprehension of morphogenesis and the development of biomaterials has significantly advanced follicle reconstruction, incorporating organ germ assembling, stem cell induction and bioprinting techniques. Despite these advancements, fully restoring hair follicles remains challenging due to the complexities of replicating embryonic signals and sustaining growth cycles. Identifying suitable cell sources for clinical applications also presents a hurdle. Here, we retrospect the progress made in the field of hair follicle regeneration, aiming to offer an exhaustive analysis on the benefits and limitations of these methods, and to foster the development of innovative solutions.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"77"},"PeriodicalIF":7.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of angiopoietin-1 signaling with engineering mesenchymal stem cells promoted efficient angiogenesis in diabetic wound healing.","authors":"Qiong Deng, Fangzhou Du, Shenzhen Pan, Yuchen Xia, Yuxin Zhu, Jingzhong Zhang, Chenglong Li, Shuang Yu","doi":"10.1186/s13287-025-04207-7","DOIUrl":"10.1186/s13287-025-04207-7","url":null,"abstract":"<p><strong>Background: </strong>Vascular insufficiency is associated with the pathogenesis and therapeutic outcomes of diabetic foot ulcers (DFU). While mesenchymal stem cells (MSCs) hold potential for DFU treatment, further enhancement in promoting angiogenesis in the challenging DFU wounds is imperative.</p><p><strong>Methods: </strong>The differential expression of pro- and anti-angiogenic factors during both normal and diabetic wound healing was compared using quantitative PCR. MSCs derived from the umbilical cord was prepared, and the engineered MSC (MSC^ANG1) overexpressing both the candidate pro-angiogenic gene, angiopoietin-1 (ANG1), and green fluorescent protein (GFP) was constructed using a lentiviral system. The pro-vascular stabilizing effects of MSC^ANG1 were assessed in primary endothelial cell cultures. Subsequently, MSC^ANG1 was transplanted into streptozotocin (STZ)-induced diabetic wound models to evaluate therapeutic effects on angiogenesis and wound healing. The underlying mechanisms were further examined both in vitro and in vivo.</p><p><strong>Results: </strong>The comprehensive analysis of the temporal expression of pro- and anti-angiogenic factors revealed a consistent impairment in ANG1 expression throughout diabetic wound healing. MSC^ANG1 exhibited robust EGFP expression in 80% of cells, with overexpression and secretion of the ANG1 protein. MSC^ANG1 notably enhanced the survival and tubulogenesis of endothelial cells and promoted the expression of junction proteins, facilitating the establishment of functional vasculature with improved vascular leakage. Although MSC^ANG1 did not enhance the survival of engrafted MSCs in diabetic wounds, it significantly promoted angiogenesis in diabetic wound healing, fostering the establishment of stable vasculature during the healing process. Activation of the protein kinase B (Akt) pathway and suppression of proto-oncogene tyrosine kinase Src (Src) activity in MSC^ANG1-treated diabetic wounds confirmed efficient angiogenesis process. Consequently, epidermal and dermal reconstruction, as well as skin appendage regeneration were markedly accelerated in MSC^ANG1-treated diabetic wounds compared to MSC-treated wounds.</p><p><strong>Conclusion: </strong>Treatment with MSCs alone promotes angiogenesis and DFU healing, while the engineering of MSCs with ANG1 provides substantial additional benefits to this therapeutic process. The engineering of MSCs with ANG1 presents a promising avenue for developing innovative strategies in managing DFU.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"75"},"PeriodicalIF":7.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apoptotic mesenchymal stem cells and their secreted apoptotic extracellular vesicles: therapeutic applications and mechanisms.","authors":"Ruoxuan Wang, Jiao Fu, Jihui He, Xinxin Wang, Wenbo Xing, Xiaojing Liu, Juming Yao, Qingsong Ye, Yan He","doi":"10.1186/s13287-025-04211-x","DOIUrl":"10.1186/s13287-025-04211-x","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs), an accessible and less ethically controversial class of adult stem cells, have demonstrated significant efficacy in treating a wide range of diseases in both the preclinical and clinical phases. However, we do not yet have a clear understanding of the mechanisms by which MSCs exert their therapeutic effects in vivo. We found that the transplanted MSCs go an apoptotic fate within 24 h in vivo irrespective of the route of administration. Still, the short-term survival of MSCs do not affect their long-term therapeutic efficacy. An increasing number of studies have demonstrated that transplantation of apoptotic MSCs (ApoMSCs) show similar or even better efficacy than viable MSCs, including a variety of preclinical disease models such as inflammatory diseases, skin damage, bone damage, organ damage, etc. Although the exact mechanism has yet to be explored, recent studies have shown that transplanted MSCs undergo apoptosis in vivo and are phagocytosed by phagocytes, thereby exerting immunomodulatory effects. The apoptotic extracellular vesicles secreted by ApoMSCs (MSC-ApoEVs) play a significant role in promoting immunomodulation, endogenous stem cell regeneration, and angiogenesis due to their apoptotic properties and inheritance of molecular characteristics from their parental MSCs. On this basis, this review aims to deeply explore the therapeutic applications and mechanisms of ApoMSCs and their secretion of MSC-ApoEVs, as well as the challenges they face.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"78"},"PeriodicalIF":7.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cell exosome therapy: current research status in the treatment of neurodegenerative diseases and the possibility of reversing normal brain aging.","authors":"Jinglan Quan, Qing Liu, Pinghui Li, Zhiyu Yang, Yaohui Zhang, Fuxing Zhao, Gaohong Zhu","doi":"10.1186/s13287-025-04160-5","DOIUrl":"10.1186/s13287-025-04160-5","url":null,"abstract":"<p><p>With the exacerbation of the aging population trend, a series of neurodegenerative diseases caused by brain aging have become increasingly common, significantly impacting the daily lives of the elderly and imposing heavier burdens on nations and societies. Brain aging is a complex process involving multiple mechanisms, including oxidative stress, apoptosis of damaged neuronal cells, chronic inflammation, and mitochondrial dysfunction, and research into new therapeutic strategies to delay brain aging has gradually become a research focus in recent years. Mesenchymal stem cells (MSCs) have been widely used in cell therapy due to their functions such as antioxidative stress, anti-inflammation, and tissue regeneration. However, accompanying safety issues such as immune rejection, tumor development, and pulmonary embolism cannot be avoided. Studies have shown that using exosome derived from mesenchymal stem cells (MSC-Exo) for the treatment of neurodegenerative diseases is a safe and effective method. It not only has the therapeutic effects of stem cells but also avoids the risks associated with cell therapy. Therefore, exploring new therapeutic strategies to delay normal brain aging from the mechanism of MSC-Exo in the treatment of neurodegenerative diseases is feasible. This review summarizes the characteristics of MSC-Exo and their clinical progress in the treatment of neurodegenerative diseases, aiming to explore the possibility and potential mechanisms of MSC-Exo in reversing brain aging.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"76"},"PeriodicalIF":7.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gain of 20q11.21 in human pluripotent stem cells enhances differentiation to retinal pigment epithelium.","authors":"Loriana Vitillo, Fabiha Anjum, Zoe Hewitt, Owen Laing, Nidaa A Ababneh, Duncan Baker, Ivana Barbaric, Peter J Coffey","doi":"10.1186/s13287-025-04196-7","DOIUrl":"10.1186/s13287-025-04196-7","url":null,"abstract":"<p><strong>Background: </strong>Cell therapies based on human pluripotent stem cells (hPSCs) are in clinical trials with the aim of restoring vision in people with age-related macular degeneration. The final cell therapy product consists of retinal pigment epithelium (RPE) cells differentiated from hPSCs. However, hPSCs recurrently acquire genetic abnormalities that give them an advantage in culture with unknown effects to the clinically-relevant cell progeny. One of the most common genetic abnormalities in hPSCs is the sub-karyotype 20q11.21 copy number variant, known to carry oncogenes. Understanding the impact of this variant on RPE differentiation and its potential for malignant transformation is crucial for the development of safe and effective cell therapies.</p><p><strong>Methods: </strong>We monitored the RPE differentiation efficiency of hPSCs with or without the 20q11.21 variant. We then phenotyped the purified RPE cells for functionality, purity and tumorigenicity potential.</p><p><strong>Results: </strong>We observed that 20q11.21 clones exhibited an enhanced differentiation capacity, developing pigmented foci at a higher rate and yield compared to normal clones. Gene expression analysis confirmed the upregulation of key RPE markers in 20q11.21 clones. The enhanced differentiation capacity of 20q11.21 clones was found to be dependent on the activity of BCL-XL, located within the amplicon. Furthermore, we demonstrated that 20q11.21-containing RPE cells displayed a mature phenotype, maintained long-term stability, and exhibited no malignant transformation capacity in vitro.</p><p><strong>Conclusion: </strong>We demonstrated that gain of 20q11.21 enhances the speed and yield of RPE differentiation without compromising the phenotype of the derivatives. Finally, we discovered that 20q11.21-localised BCL-XL is important for RPE differentiation with potential non-canonical roles in retinal biology.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"82"},"PeriodicalIF":7.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human spindle-shaped urine-derived stem cell exosomes alleviate severe fatty liver ischemia-reperfusion injury by inhibiting ferroptosis via GPX4.","authors":"Shangheng Shi, Cunle Zhu, Shangxuan Shi, Xinqiang Li, Imran Muhammad, Qingguo Xu, Xinwei Li, Ziyin Zhao, Huan Liu, Guangming Fu, Meiying Song, Xijian Huang, Feng Wang, Jinzhen Cai","doi":"10.1186/s13287-025-04202-y","DOIUrl":"10.1186/s13287-025-04202-y","url":null,"abstract":"<p><strong>Background: </strong>Severe hepatic steatosis can exacerbate Ischemia-reperfusion injury (IRI), potentially leading to early graft dysfunction and primary non-function. In this study, we investigated the heterogeneity of different subpopulations of Urine-derived stem cells (USCs) to explore the most suitable cell subtype for treating severe steatotic liver IRI.</p><p><strong>Methods: </strong>This study utilized scRNA-seq and Bulk RNA-seq to investigate the transcriptional heterogeneity between Spindle-shaped USCs (SS-USCs) and Rice-shaped USCs (RS-USCs). Additionally, rat fatty Liver transplantation (LT) model, mouse fatty liver IRI model, and Steatotic Hepatocyte Hypoxia-Reoxygenation (SHP-HR) model were constructed. Extracellular vesicles derived from SS-USCs and RS-USCs were isolated and subjected to mass spectrometry analysis. The therapeutic effects of Spindle-shaped USCs Exosomes (SS-USCs-Exo) and Rice-shaped USCs Exosomes (RS-USCs-Exo) were explored, elucidating their potential mechanisms in inhibiting ferroptosis and alleviating IRI.</p><p><strong>Results: </strong>Multiple omics analyses confirmed that SS-USCs possess strong tissue repair and antioxidant capabilities, while RS-USCs have the potential to differentiate towards specific directions such as the kidney, nervous system, and skeletal system, particularly showing great application potential in renal system reconstruction. Further experiments demonstrated in vivo and in vitro models confirming that SS-USCs and SS-USCs-Exo significantly inhibit ferroptosis and alleviate severe fatty liver IRI, whereas the effects of RS-USCs/RS-USCs-Exo are less pronounced. Analysis comparing the proteomic differences between SS-USCs-Exo and RS-USCs-Exo revealed that SS-USCs-Exo primarily inhibit ferroptosis and improve cellular viability by secreting exosomes containing Glutathione Peroxidase 4 (GPX4) protein. This highlights the most suitable cell subtype for treating severe fatty liver IRI.</p><p><strong>Conclusions: </strong>SS-USCs possess strong tissue repair and antioxidant capabilities, primarily alleviating ferroptosis in the donor liver of fatty liver through the presence of GPX4 protein in their exosomes. This highlights SS-USCs as the most appropriate cell subtype for treating severe fatty liver IRI.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"81"},"PeriodicalIF":7.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes from adipose-derived stem cells accelerate wound healing by increasing the release of IL-33 from macrophages.","authors":"Yichen Wang, Hongfan Ding, Ruiqi Bai, Qiang Li, Boyuan Ren, Pianpian Lin, Chengfei Li, Minliang Chen, Xiao Xu","doi":"10.1186/s13287-025-04203-x","DOIUrl":"10.1186/s13287-025-04203-x","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cell (MSC) -derived exosomes, especially adipose-derived mesenchymal stem cell exosomes (ADSC-Exos), have emerged as a promising alternative for skin damage repair with anti-inflammatory, angiogenic and cell proliferation effects while overcoming some of the limitations of MSC. However, the mechanism by which ADSC-Exos regulates inflammatory cells during wound healing remains unclear. This study investigated how ADSC-Exos regulate macrophages to promote wound healing.</p><p><strong>Methods: </strong>ADSC-Exos were isolated using ultracentrifugation, with subsequent quantification of exosomes particle number. To investigate their role in wound healing, the effects of ADSC-Exos on inflammation, angiogenesis, collagen deposition and macrophage polarization were evaluated through immunohistochemical staining, immunofluorescence and western blotting. Changes in gene expression associated with ADSC-Exos-induced macrophage polarization were analyzed using qPCR. RNA sequencing was performed to identify differentially expressed genes affected by ADSC-Exos. The critical role of IL-33 in the wound healing process was further confirmed using Il33^-/- mice. Additionally, co-culture experiments were conducted to explore the effects of IL-33 on keratinocyte proliferation, collagen deposition and epithelialization.</p><p><strong>Results: </strong>ADSC-Exos inhibited the expression of TNF-α and IL-6, induced M2 macrophage polarization, promoted collagen deposition and angiogenesis, and accelerated wound healing. RNA sequencing identified IL-33 as a key mediator in this process. In Il33^-/- mice, impaired wound healing and decreased M2 macrophage polarization were observed. The co-culture experiments showed that IL-33 enhanced keratinocyte function through activation of the Wnt/β-catenin signaling pathway. These findings highlight the therapeutic potential of ADSC-Exos in wound healing by modulating IL-33.</p><p><strong>Conclusions: </strong>ADSC-Exos promote wound healing by regulating macrophage polarization and enhancing IL-33 release which drives keratinocyte proliferation, collagen deposition and epithelialization via the Wnt/β-catenin signaling pathway. These findings provide a mechanistic basis for the therapeutic potential of ADSC-Exos in tissue repair and regeneration.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"80"},"PeriodicalIF":7.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Adenovirus-mediated transfer of hepatocyte growth factor gene to human dental pulp stem cells under good manufacturing practice improves their potential for periodontal regeneration in swine.","authors":"Yu Cao, Zhenhai Liu, Yilin Xie, Jingchao Hu, Hua Wang, Zhipeng Fan, Chunmei Zhang, Jingsong Wang, Chu-Tse Wu, Songlin Wang","doi":"10.1186/s13287-025-04214-8","DOIUrl":"10.1186/s13287-025-04214-8","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"73"},"PeriodicalIF":7.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Adra2α expression of adipose stem cells on the treatment of type 2 diabetic mice.","authors":"Xinzhen Zuo, Gaofan Meng, Lili Song, Xiao Dong","doi":"10.1186/s13287-025-04192-x","DOIUrl":"10.1186/s13287-025-04192-x","url":null,"abstract":"<p><strong>Background: </strong>Adipose stem cell (ASC) therapy has been tested as a new option for the treatment of type 2 diabetes (T2D). Our previous transcriptome sequencing analysis showed that the adrenergic α2 receptor (Adra2α) was highly expressed in ASCs from T2D mice compared to healthy controls. This study aims to explore the role of Adra2α on the characterization and therapeutic function of ASCs.</p><p><strong>Methods: </strong>Clonidine (an Adra2α agonist) or si-RNA was used to observe Adra2α on ASCs proliferation, migration, growth factors (HGF, TGF-β1 and VEGF) expression and secretion. T2D mice were treated with non-treated control or Adra2α knockdown T2D ASCs (namely NC ASCs or KD ASCs). Mice glucose levels, insulin sensitivity and other metabolic indicators were measured and compared.</p><p><strong>Results: </strong>Treatment of ASCs with Clonidine reduced the proliferation, migration, and growth factors expression and secretion of ASCs, while Adra2α knocking down ASCs showed opposite effects. This translated in vivo when T2D + KD ASCs could improve hyperglycemia and insulin resistance, reduce fat content in adipose tissues and livers, suppress body inflammation, and increase pancreatic β cell mass in T2D mice compared to NC ASCs.</p><p><strong>Conclusions: </strong>Adra2α plays a critical role in regulating the proliferation, migration, and expression of growth factors of ASCs. Suppression of Adra2α expression in T2D ASCs restored/improved their therapeutic effects.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"72"},"PeriodicalIF":7.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}