Willem Delabie, Gabriele Boretti, Stephanie A Groot, Davina Ardanary, Olafur Sigurjónsson, Thomas R L Klei, Philippe Vandekerckhove, Hendrik B Feys
{"title":"Human platelet lysate standardization across three independent European blood establishments.","authors":"Willem Delabie, Gabriele Boretti, Stephanie A Groot, Davina Ardanary, Olafur Sigurjónsson, Thomas R L Klei, Philippe Vandekerckhove, Hendrik B Feys","doi":"10.1186/s13287-025-04445-9","DOIUrl":"10.1186/s13287-025-04445-9","url":null,"abstract":"<p><p>Human platelet lysate (hPL) is a clinically safe alternative to fetal bovine serum (FBS). However, variability in blood donation practices, platelet concentrate preparation methods, storage and hPL manufacturing complicates standardization across jurisdictions. This study aimed to establish a first multinational hPL manufacturing standardization across three European blood centers to test feasibility and variability. A single batch of hPL production sets was distributed to the participating centers. There, hPL was produced following a single standard operating protocol but starting from each center's unique platelet concentrates. Each center prepared four 'national' hPL batches and four 'international' batches. Researchers conducted blinded quality and variation analyses to ensure unbiased results. All hPL batches exhibited comparable total protein levels, pH, ionic strength, and lactate content. Analysis of twelve growth factors showed minor variations across batches. Endothelial cell outgrowth and wound closure were slower in hPL than FBS but remained consistent across batches. Mesenchymal stem cell (MSC) doubling was significantly faster in hPL than in FBS, with MSC phenotype consistency confirmed via flow cytometry. Differentiation into adipogenic and osteogenic tissue was successful in all hPL samples. The inter-institutional variation across all national batches was higher for all critical outcome parameters compared to the variation in the four international batches. These findings confirm the feasibility of manufacturing standardized hPL across borders and show lower variability when doing so. This supports further efforts to stabilize hPL supply and advance cytotherapy standardization in Europe.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"329"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544933","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}
Yanxia Chen, Meijuan He, Lei Cui, Jianguo Zhang, Hanpeng Huang, Zhimin Tao
{"title":"MiR-145 encapsulated small extracellular vesicles inhibit colorectal cancer progression by downregulating fascin actin-bundling protein 1 expression.","authors":"Yanxia Chen, Meijuan He, Lei Cui, Jianguo Zhang, Hanpeng Huang, Zhimin Tao","doi":"10.1186/s13287-025-04456-6","DOIUrl":"10.1186/s13287-025-04456-6","url":null,"abstract":"<p><strong>Background: </strong>Drug degradation poses a significant challenge in the pursuit of effective gene therapies for cancers.</p><p><strong>Methods: </strong>Here we have developed a bioactive nanosized composite that utilizes human umbilical cord mesenchymal stem cells (hucMSCs) derived small extracellular vesicles (sEVs), to carry tumor suppressor miR-145 alongside erbium-doped rare earth nanoparticles (ErNPs). This approach not only enhances in vivo delivery but also facilitates real-time fluorescence tracking of nucleic acid drugs in the near infrared (NIR) II window. With this technique, we are able to realize and visualize the effective inhibition of colorectal cancer (CRC) progression in a xenografted murine model.</p><p><strong>Results: </strong>Our results revealed that the efficient loading of miR-145 into sEVs could be achieved through a dynamic combination of sonication and electroporation. The resulting miR-145-encapsulated sEVs (i.e., miRNA@sEVs) exhibited a profound ability to hinder tumor growth by effectively downregulating the expression of fascin actin-bundling protein 1 (FSCN1), both in vitro and in vivo. Additionally, the circulation half-time of miRNA@sEVs was measured to be ~ 4 h and the fluorescence at the tumor sites reached a peak intensity at ~ 8 h after intravenous injection of sEVs particles. Finally, the fluorescent signals of miRNA@sEVs were predominantly localized in the mouse liver and spleen, with substantial accumulation in tumors.</p><p><strong>Conclusions: </strong>Our results illuminated the excellent biosafety of miRNA@sEVs and their high accumulation in tumors, leading to efficient suppression of tumor progression. This research heralds a promising advancement in gene therapy, paving the way for more effective and safer treatment options.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"343"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544938","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}
Jannette Rodríguez-Pallares, Lucia A Garcia-Crivaro, Juan A Parga, Jose Luis Labandeira-Garcia
{"title":"Renin-angiotensin system as an emerging target to modulate adult neurogenesis in health and disease.","authors":"Jannette Rodríguez-Pallares, Lucia A Garcia-Crivaro, Juan A Parga, Jose Luis Labandeira-Garcia","doi":"10.1186/s13287-025-04430-2","DOIUrl":"10.1186/s13287-025-04430-2","url":null,"abstract":"<p><p>Adult neurogenesis is a complex multiphase process involving the formation and integration of new neurons into existing brain circuits. Although it was first described over 50 years ago and numerous factors involved in regulating neurogenic niches have been extensively studied, the underlying molecular mechanisms and interactions involved in controlling adult neurogenesis are still not fully understood. The renin-angiotensin system (RAS) is a well-known hormonal system that controls water and electrolyte balance and blood pressure. In addition to the circulating RAS, a local brain RAS has been described, with a key role in brain homeostasis. A wealth of evidence has emerged showing the involvement of RAS in neurodegeneration and neuroinflammation as well as in proliferation, differentiation, survival, and regeneration processes. Moreover, RAS has a role in cognitive function, behavioral responses, and dementia, which are closely related to neurogenic areas. This review summarizes the current evidence on the role of RAS in regulating adult neurogenic niches. We critically discuss pre-clinical and clinical studies investigating the role of RAS as a potential therapeutic target to modulate neurogenesis in pathological conditions.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"332"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544942","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}
Lingxiao Wang, Yang Liu, Zhanqiu Diao, Yishu Huang, Haoqing Yang, Yue Zhang, Bowen Zhou, Zhenhua Gao, Zhaochen Shan, Jun Li, Zhipeng Fan
{"title":"The circ_0054633/miR-590-3p/RUNX2 positive feedback loop promotes the osteogenic differentiation of BMSCs.","authors":"Lingxiao Wang, Yang Liu, Zhanqiu Diao, Yishu Huang, Haoqing Yang, Yue Zhang, Bowen Zhou, Zhenhua Gao, Zhaochen Shan, Jun Li, Zhipeng Fan","doi":"10.1186/s13287-025-04450-y","DOIUrl":"10.1186/s13287-025-04450-y","url":null,"abstract":"<p><strong>Background: </strong>Mandibular bone marrow stem cells (BMSCs) from patients with type 2 diabetes mellitus (T2DM) have poor osteogenic differentiation capacity. Elucidating the molecular mechanisms by which circular RNAs (circRNAs) play specific roles in T2DM will reveal new diagnostic biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>BMSCs with different circ_0054633 expression levels were generated. Furthermore, alkaline phosphatase (ALP) activity, alizarin red staining (ARS), and transplantation of HA/tricalcium phosphate into BMSCs were performed to detect the osteogenic effects of different levels of circ_0054633 expression in BMSCs in vivo and in vitro.</p><p><strong>Results: </strong>In this study, we identified 80 differentially expressed circRNAs in jawbone-derived BMSCs from patients with T2DM. Notably, significant downregulation of circ_0054633 promoted the osteogenic differentiation of these cells in vitro and in vivo. Mechanistically, circ_0054633 acts as a miRNA sponge; specifically, it actively regulates the expression of RUNX2 by sponging miR-590-3p and thus promoting the osteogenic differentiation of the BMSCs. In addition, we found that circ_0054633 was a direct transcriptional target of RUNX2. RUNX2 overexpression activated the circ_0054633 promoter and promoted the generation of nuclear circ_0054633, whereas RUNX2 knockdown abrogated the osteogenic role of circ_0054633 and formed a circ_005463/miR-590-3p/RUNX2 positive feedback loop.</p><p><strong>Conclusions: </strong>Our results suggest that the circ_0054633/miR-590-3p/RUNX2 positive feedback loop promotes the osteogenic differentiation of BMSCs and is expected to be a potential biomarker and therapeutic target for bone regeneration in T2DM.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"325"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544946","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":"Production of bioactive cytokines using plant expression system for cardiovascular cell differentiation from human pluripotent stem cells.","authors":"Kozue Murata, Kanae Takamura, Risa Watanabe, Akitomo Nagashima, Miho Miyauchi, Yoshiteru Miyauchi, Hidetoshi Masumoto","doi":"10.1186/s13287-025-04424-0","DOIUrl":"10.1186/s13287-025-04424-0","url":null,"abstract":"<p><p>Bioactive cytokines such as vascular endothelial growth factor (VEGF) and Activin A are critical for the differentiation of stem cells into vascular endothelial cells and cardiomyocytes. However, production of the cytokines using conventional Escherichia coli or mammalian cell expression systems carries risks of immunogenicity and viral contamination. In this study, we developed a VEGF and Activin A plant expression system and demonstrated that plant-expressed VEGF and Activin A are as active as their commercial counterparts. We also showed that plant-expressed VEGF and Activin A are as efficient as human recombinant counterparts in inducing endothelial cells and cardiomyocytes from human pluripotent stem cells. These results suggest that plant-expressed VEGF and Activin A are promising alternatives for the safe and efficient production of cardiac cells, specifically cardiomyocytes and endothelial cells, for stem cell-based regenerative medicine.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"303"},"PeriodicalIF":7.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485701","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":"LINC01013 reverses bisphosphonate-impaired osteogenic differentiation of JBMMSCs by regulating intracellular translocation of ILF3.","authors":"Jiaxin Song, Wanqing Wang, Xuanhe Feng, Haoqing Yang, Zhaochen Shan, Zhipeng Fan","doi":"10.1186/s13287-025-04467-3","DOIUrl":"10.1186/s13287-025-04467-3","url":null,"abstract":"<p><strong>Background: </strong>Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication associated with bisphosphonate (BP) therapy. Enhancement of the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (JBMMSCs) is a key issue in the treatment of BRONJ. In this study, we investigated the role and mechanism of LINC01013 in regulating osteogenic differentiation of JBMMSCs.</p><p><strong>Methods: </strong>Osteogenic differentiation of JBMMSCs was assessed in vitro using alkaline phosphatase (ALP), alizarin red staining (ARS), and western blotting. JBMMSCs transplanted into the backs of nude mice were used to detect JBMMSCs osteogenesis in vivo. Molecular mechanisms involved in JBMMSCs osteogenesis were evaluated using real-time fluorescence quantitative polymerase chain reaction, western blotting, fluorescence in situ hybridization, RNA pull-down, and RNA-seq.</p><p><strong>Results: </strong>Homeobox C8 (HOXC8) knockdown enhanced ALP activity, ARS, and expression of bone sialoprotein and osteocalcin in JBMMSCs under normal and BP stimulation conditions. HOXC8 negatively regulated LINC01013 expression. LINC01013 enhanced JBMMSCs osteogenic differentiation impaired by BP stimulation. Furthermore, LINC01013 regulated the expression of inflammation-related genes in JBMMSCs under BP conditions. LINC01013 formed a complex with ILF3. Two isoforms of ILF3 (NF90 and NF110) promoted the osteogenic differentiation of JBMMSCs under normal and BP conditions, depending on their nuclear localization. Additionally, NF90, which is located in the nucleus, inhibited the expression of NLR family pyrin domain containing 3 (NLRP3).</p><p><strong>Conclusions: </strong>In summary, HOXC8 negatively regulates LINC01013 to inhibit osteogenic differentiation of JBMMSCs under BP conditions. We also further clarified that LINC01013 binding to ILF3 affects ILF3 nuclear localization to regulate JBMMSCs osteogenic differentiation and regulates NLRP3/Caspase-1 pathway to affect JBMMSCs function under BP stimulation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"319"},"PeriodicalIF":7.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476741","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}
Jing-Yan Cheng, Hui-Yun Cheng, Jung-Tung Hung, Gonzalo Mallarino Restrepo, Shih-Pin Chiou, Ling-Yi Shih, Alice L Yu, Huang-Kai Kao, John Yu, Fu-Chan Wei
{"title":"Enhancing retention and quality of tissue stromal vascular fraction graft with globo H ceramide.","authors":"Jing-Yan Cheng, Hui-Yun Cheng, Jung-Tung Hung, Gonzalo Mallarino Restrepo, Shih-Pin Chiou, Ling-Yi Shih, Alice L Yu, Huang-Kai Kao, John Yu, Fu-Chan Wei","doi":"10.1186/s13287-025-04395-2","DOIUrl":"10.1186/s13287-025-04395-2","url":null,"abstract":"<p><strong>Background: </strong>Fat grafting has been extensively used in plastic surgery practice, yet unstable retention in the recipient site remains a significant clinical challenge. The limited tolerance of injected adipose tissue to ischemia has prompted strategies aiming at timely enhancing the vascularity of the grafted fat. Various modified fat graft preparations have been used, and the mechanically processed tissue stromal vascular fraction (tSVF) derived from fat tissue has garnered considerable interest for enhancing rate of fat graft retention. Further enhancement of the graft retention and quality through supplements to tSVF is worthy of investigation.</p><p><strong>Methods: </strong>The arteriovenous (AV) shunt in rats has been used to evaluate tSVF in vivo. We employed this animal model to investigate the regenerative potential of glycolipid Globo H Ceramide (GHCer) added to tSVF isolated from male Lewis rats. Sixty-two rats divided into four groups were studied. Study parameters included gene expression of vascular endothelial growth factor A (VEGFA) and fatty acid binding protein 4 (FABP4), percentages of the CD45<sup>-</sup>CD31<sup>+</sup> endothelial cell, fat tissue retention and fibrotic changes. In vitro studies on adipose-derived mesenchymal stromal cells (AD-MSCs) included angiogenesis by tube formation assay and adipogenesis.</p><p><strong>Results: </strong>The addition of GHCer resulted in superior retention of the tSVF grafts at one-, two-, and eight-week post-grafting (p < 0.05). Elevated expression VEGFA was observed from one week (p < 0.05), followed by FABP4 at two weeks post-grafting in the tSVF + GHCer grafts (p < 0.01). After eight weeks, the numbers of CD45<sup>-</sup>CD31<sup>+</sup> endothelial cells and adipocytes were significantly increased in the tSVF + GHCer grafts (p < 0.01), while collagen deposition was reduced (p < 0.05). Given that GHCer potentially exerted its effects on tSVF through AD-MSCs within, we performed in vitro studies and demonstrated that GHCer promoted AD-MSC differentiation into neovessels (p < 0.05) and adipocytes (p < 0.001).</p><p><strong>Conclusions: </strong>Supplementing GHCer to tSVF effectively reduced fat reabsorption and fibrotic changes of the grafts, while enhancing angiogenesis and adipogenesis, potentially through facilitating AD-MSC differentiation within tSVF. These findings support the potential clinical application of GHCer to enhance the stability and long-term outcomes of fat grafting procedures.</p><p><strong>Trial registration: </strong>Not applicable.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"317"},"PeriodicalIF":7.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476740","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}
Siti Zawiah Abdul Malik, Yugashini Muhilan, Fazlina Nordin, Min Hwei Ng, Jia Xian Law, Siti A M Imran, Izyan Mohd Idris, Gee Jun Tye
{"title":"Stem cell derived exosome trilogy: an epic comparison of human MSCs, ESCs and iPSCs.","authors":"Siti Zawiah Abdul Malik, Yugashini Muhilan, Fazlina Nordin, Min Hwei Ng, Jia Xian Law, Siti A M Imran, Izyan Mohd Idris, Gee Jun Tye","doi":"10.1186/s13287-025-04440-0","DOIUrl":"10.1186/s13287-025-04440-0","url":null,"abstract":"<p><p>Exosomes, containing molecular constituents of their cell of origin, including proteins and nucleic acids, were first discovered in immature red blood cells in 1983. Excellent intercell communication can be achieved by shuttling these various molecules between cells. Stem cell-derived exosomes (SC-Exos) contain paracrine-soluble factors that play important roles in tissue development, homeostasis, and regeneration. This paracrine activity of SC-Exos has been found to be a predominant mechanism by which stem cell-based therapies mediate their effects on degenerative, autoimmune and/or inflammatory diseases. Compared to other types of stem cells, human embryonic stem cells (hESCs), human induced pluripotent stem cells (hiPSCs), human mesenchymal stem cells (hMSCs) are the most popular because of their efficient immunomodulatory effects. The advantages and disadvantages of using exosomes isolated from the stem cell trio for therapeutic applications are further discussed in this review.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"318"},"PeriodicalIF":7.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476743","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":"Distal electrical stimulation enhances neuromuscular reinnervation and satellite cell differentiation for functional recovery.","authors":"Chun-Wei Lin, Szu-Han Chen, Siao Muk Cheng, Tzu-Chun Chung, Wentai Liu, Daw-Yang Hwang, Song Li, Sheng-Che Lin, Yuan-Yu Hsueh","doi":"10.1186/s13287-025-04459-3","DOIUrl":"10.1186/s13287-025-04459-3","url":null,"abstract":"<p><strong>Background: </strong>Peripheral nerve injuries lead to significant motor deficits, with limited treatment options for full functional recovery. Distal electrical stimulation (E-stim) has shown promise in promoting neuromuscular reinnervation, though its mechanisms are not yet fully understood. This study aims to investigate the regulatory effects of distal E-stim on neuromuscular junction (NMJ) reinnervation and Satellite cell activity in denervated muscle injury.</p><p><strong>Methods: </strong>Using a sciatic nerve critical gap model in Sprague-Dawley rats (8-week-old, random sex), we applied distal E-stim and assessed neuromuscular and functional recovery through histological, biochemical, and functional evaluations over six weeks. The Sciatic Function Index (SFI) was measured at baseline and at subsequent time points post-injury. We quantified muscle mass, NMJ morphology, and neurotransmitter levels (acetylcholine and acetylcholinesterase), and analyzed muscle fiber electrophysiology using single-muscle electromyography to assess denervated muscle autoelectricity. Additionally, single-cell RNA sequencing was performed to examine gene expression in Satellite cells.</p><p><strong>Results: </strong>Distal E-stim significantly enhanced neuromuscular reinnervation, as evidenced by improved SFI scores, increased muscle mass, and reduced muscle atrophy. Histological analysis showed larger muscle fiber cross-sectional areas and enhanced NMJ structure. Elevated levels of acetylcholine and acetylcholinesterase, along with reduced fibrillation potentials in muscle fibers, further indicated preserved NMJ function. Single-cell RNA sequencing revealed upregulation of genes associated with muscle differentiation and angiogenesis in Satellite cell clusters, suggesting that distal E-stim fosters a regenerative environment.</p><p><strong>Conclusions: </strong>Our findings demonstrate that distal E-stim promotes functional recovery through NMJ preservation and Satellite cell differentiation, offering novel insights into molecular mechanisms that may enhance electroceutical therapies for peripheral nerve injuries. Further research could optimize E-stim protocols to maximize clinical benefits for patients with neuromuscular impairments.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"322"},"PeriodicalIF":7.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476739","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}
Paula Barlabé, Xabier L Aranguren, Giulia Coppiello
{"title":"Blastocyst complementation: current progress and future directions in xenogeneic organogenesis.","authors":"Paula Barlabé, Xabier L Aranguren, Giulia Coppiello","doi":"10.1186/s13287-025-04426-y","DOIUrl":"10.1186/s13287-025-04426-y","url":null,"abstract":"<p><p>The generation of organs derived from pluripotent stem cells can be achieved in vivo through the blastocyst complementation technique. This method is based on the introduction of pluripotent stem cells into organogenesis-disabled pre-implantation embryos, where environmental signals instruct donor cells to colonize the vacant niche and to develop into the missing organ. When applied interspecies, this approach has the potential to produce human organs in genetically engineered livestock, offering a promising solution to the global transplants' shortage crisis. In this review, we summarize the current progress in blastocyst complementation research and highlight the key challenges that must be addressed to advance this field.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"321"},"PeriodicalIF":7.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476738","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}