Stem Cell Research & Therapy最新文献

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Mesenchymal stem cell exosome therapy: current research status in the treatment of neurodegenerative diseases and the possibility of reversing normal brain aging.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-21 DOI: 10.1186/s13287-025-04160-5
Jinglan Quan, Qing Liu, Pinghui Li, Zhiyu Yang, Yaohui Zhang, Fuxing Zhao, Gaohong Zhu
{"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}
引用次数: 0
Gain of 20q11.21 in human pluripotent stem cells enhances differentiation to retinal pigment epithelium.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-21 DOI: 10.1186/s13287-025-04196-7
Loriana Vitillo, Fabiha Anjum, Zoe Hewitt, Owen Laing, Nidaa A Ababneh, Duncan Baker, Ivana Barbaric, Peter J Coffey
{"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}
引用次数: 0
Human spindle-shaped urine-derived stem cell exosomes alleviate severe fatty liver ischemia-reperfusion injury by inhibiting ferroptosis via GPX4.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-21 DOI: 10.1186/s13287-025-04202-y
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
{"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}
引用次数: 0
Exosomes from adipose-derived stem cells accelerate wound healing by increasing the release of IL-33 from macrophages.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-21 DOI: 10.1186/s13287-025-04203-x
Yichen Wang, Hongfan Ding, Ruiqi Bai, Qiang Li, Boyuan Ren, Pianpian Lin, Chengfei Li, Minliang Chen, Xiao Xu
{"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<sup>-/-</sup> 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<sup>-/-</sup> 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}
引用次数: 0
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.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-20 DOI: 10.1186/s13287-025-04214-8
Yu Cao, Zhenhai Liu, Yilin Xie, Jingchao Hu, Hua Wang, Zhipeng Fan, Chunmei Zhang, Jingsong Wang, Chu-Tse Wu, Songlin Wang
{"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}
引用次数: 0
Effects of Adra2α expression of adipose stem cells on the treatment of type 2 diabetic mice.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-14 DOI: 10.1186/s13287-025-04192-x
Xinzhen Zuo, Gaofan Meng, Lili Song, Xiao Dong
{"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}
引用次数: 0
Endoplasmic reticulum stress and rhodopsin accumulation in an organoid model of Retinitis Pigmentosa carrying a RHO pathogenic variant.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-14 DOI: 10.1186/s13287-025-04199-4
Arnau Navinés-Ferrer, Esther Pomares
{"title":"Endoplasmic reticulum stress and rhodopsin accumulation in an organoid model of Retinitis Pigmentosa carrying a RHO pathogenic variant.","authors":"Arnau Navinés-Ferrer, Esther Pomares","doi":"10.1186/s13287-025-04199-4","DOIUrl":"10.1186/s13287-025-04199-4","url":null,"abstract":"<p><strong>Background: </strong>Retinitis Pigmentosa (RP) is the most prevalent inherited retinal dystrophy, with more than 120 causative genes. Among them, RHO was the first photoreceptor gene described to harbor mutations responsible for RP. RHO pathogenic variants usually induce a dominant negative effect in which the accumulation of misfolded rhodopsin protein leads to ER stress, autophagy and lastly rod photoreceptor death.</p><p><strong>Methods: </strong>We differentiated photoreceptor precursors and retinal organoids from an iPSC line of a patient carrying the Pro215Leu mutation in RHO gene. Both cell models were analyzed to determine their maturation, the expression and localization of RHO mRNA and the rhodopsin protein and the activation of autophagy or ER pathways.</p><p><strong>Results: </strong>The Pro215Leu mutation causes rhodopsin accumulation in the soma of rod photoreceptor precursors along with a faster recycling by the proteasome. In both precursors and retinal organoids, we observed autophagy defects and late endoplasmic reticulum stress through CHOP increase.</p><p><strong>Conclusions: </strong>Unraveling the molecular pathophysiology of these mutations is key for understanding the basis of the disease and design proper gene and cell therapies for its treatment.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"71"},"PeriodicalIF":7.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415301","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}
引用次数: 0
Construction of tetravalent bispecific Tandab (CD3/BCMA)-secreting human umbilical cord mesenchymal stem cells and its efficiency in the treatment of multiple myeloma.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-12 DOI: 10.1186/s13287-025-04212-w
Mengshang Xiong, Chunfang Kong, Yang Lu, Jiaojun Liu, Weirong Ding, Tingting Zhang, Wei Zuo, Lixia Cao, Qiling Lu, Anna Li, Chaoyu Li, Liting Ding, Yutao Yan, Bo Ke, Caishui Wan
{"title":"Construction of tetravalent bispecific Tandab (CD3/BCMA)-secreting human umbilical cord mesenchymal stem cells and its efficiency in the treatment of multiple myeloma.","authors":"Mengshang Xiong, Chunfang Kong, Yang Lu, Jiaojun Liu, Weirong Ding, Tingting Zhang, Wei Zuo, Lixia Cao, Qiling Lu, Anna Li, Chaoyu Li, Liting Ding, Yutao Yan, Bo Ke, Caishui Wan","doi":"10.1186/s13287-025-04212-w","DOIUrl":"10.1186/s13287-025-04212-w","url":null,"abstract":"<p><strong>Background: </strong>Highly efficient targeted therapy is urgently needed for multiple myeloma (MM). Mesenchymal stem cells (MSCs) are an attractive candidate of cell-based, targeted therapy due to their inherent tumor tropism. However, there is still no MSCs-based tandem diabody for treating MM.</p><p><strong>Methods: </strong>Here, we designed a dual-target therapeutic system in which human umbilical cord MSCs (UCMSCs) were engineered to produce and deliver Tandab (CD3/BCMA), a tetravalent bispecific tandem diabody with two binding sites for CD3 and two for B-cell maturation antigen (BCMA). Western blot and flow cytometry were used to confirm the lentivirus-mediated construction of UCMSCs for diabody expression. The tropism of MSCs towards H929 cells in vitro was determined by migration assays, and the in vivo homing capacity of MSCs was analyzed by immunofluorescence staining. The activation and antitumor efficacy of human T cells mediated by MSCs secreting Tandab (CD3/BCMA) were evaluated in vitro. Finally, an MM xenograft NOD/SCID mouse model was established to investigate the therapeutic effect in vivo.</p><p><strong>Results: </strong>We successfully constructed MSCs that can continuously secrete bioactive Tandab (CD3/BCMA), whereby lentiviral transduction did not affect the morphology, proliferation, and lineage differentiation potential of the MSCs. The tropism of MSC-Tandab for MM was verified both in vitro and in vivo. Furthermore, MSC-Tandab promoted the expansion and activation of primary human T cells and induced healthy donor T cells to selectively eliminate BCMA-positive cell lines and primary blasts from patients but not BCMA-negative cells. A similar ability was also observed in the patient-derived T cells. Finally, MSC-Tandab significantly alleviated the MM xenograft tumor burden in NOD/SCID mice without toxic side effects in vivo, whereby the cytokine levels (IFN-γ) in the peripheral blood (PB) were higher in the MSC-Tandab group, and the tumor infiltration of T cells was significantly enhanced.</p><p><strong>Conclusions: </strong>These results suggest that UCMSCs releasing Tandab (CD3/BCMA) are a promising new tool for the treatment of MM, opening a new avenue for the development of cell-based therapy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"69"},"PeriodicalIF":7.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410981","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}
引用次数: 0
Pericyte-derived extracellular vesicles improve vascular barrier function in sepsis via the Angpt1/PI3K/AKT pathway and pericyte recruitment: an in vivo and in vitro study.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-12 DOI: 10.1186/s13287-025-04201-z
Zi-Sen Zhang, Ao Yang, Xi Luo, He-Nan Zhou, Yi-Yan Liu, Dai-Qin Bao, Jie Zhang, Jia-Tao Zang, Qing-Hui Li, Tao Li, Liang-Ming Liu
{"title":"Pericyte-derived extracellular vesicles improve vascular barrier function in sepsis via the Angpt1/PI3K/AKT pathway and pericyte recruitment: an in vivo and in vitro study.","authors":"Zi-Sen Zhang, Ao Yang, Xi Luo, He-Nan Zhou, Yi-Yan Liu, Dai-Qin Bao, Jie Zhang, Jia-Tao Zang, Qing-Hui Li, Tao Li, Liang-Ming Liu","doi":"10.1186/s13287-025-04201-z","DOIUrl":"10.1186/s13287-025-04201-z","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles derived from pericytes (PCEVs) have been shown to improve vascular permeability, with their therapeutic effects attributed to the presence of pro-regenerative molecules. We hypothesized that angiopoietin 1 (Angpt1) carried by PCEVs contributes to their therapeutic effects after sepsis.</p><p><strong>Methods: </strong>A cecal ligation and puncture (CLP)-induced sepsis rat model was used in vivo, and the effects of PCEVs on vascular endothelial cells were studied in vitro. First, proteomic and Gene Ontology enrichment analyses were performed to analyze the therapeutic mechanism of PCEVs, revealing that the angiogenesis-related protein Angpt1 was highly expressed in PCEVs. We then down-regulated Angpt1 in PCEVs. The role of PCEV-carried Angpt1 on intestinal barrier function, PCs recruitment, and inflammatory cytokines was measured by using septic Sprague-Dawley rats and platelet-derived growth factor receptor beta (PDGFR-β)-Cre + mT/mG transgenic mice.</p><p><strong>Results: </strong>PCEVs significantly improved vascular permeability, proliferation, and angiogenesis in CLP-induced gut barrier injury both in vivo and in vitro. Further studies have shown that PCEVs exert a protective effect on intestinal barrier function and PC recruitment. Additionally, PCEVs reduced serum inflammatory factor levels. Our data also demonstrated that the protein levels of phospho-PI3K and phospho-Akt both increased after PCEVs administration, whereas knocking out Angpt1 suppressed the protective effects of PCEVs through decreased activation of PI3K/Akt signaling.</p><p><strong>Conclusion: </strong>PCEVs protect against sepsis by regulating the vascular endothelial barrier, promoting PC recruitment, protecting intestinal function, and restoring properties via activation of the Angpt1/PI3K/AKT pathway.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"70"},"PeriodicalIF":7.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411008","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}
引用次数: 0
Pyroptosis: candidate key targets for mesenchymal stem cell-derived exosomes for the treatment of bone-related diseases.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-12 DOI: 10.1186/s13287-025-04167-y
Haiming Li, Peng Zhang, Minghui Lin, Kang Li, Cunxin Zhang, Xiao He, Kai Gao
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