Stem Cell Research & Therapy最新文献

{"title":"Human umbilical cord mesenchymal stem cell-derived microvesicles alleviate pulmonary fibrosis by inhibiting monocyte‒macrophage migration through ERK1/2 signaling-mediated suppression of CCL2 expression.","authors":"Xiuping Liang, Yanhong Li, Yinlan Wu, Tong Wu, Deying Huang, Ziyi Tang, Lu Cheng, Chunyu Tan, Ronghui Liao, Jing Zhao, Zehui Liao, Yubin Luo, Yi Liu","doi":"10.1186/s13287-025-04266-w","DOIUrl":"10.1186/s13287-025-04266-w","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary fibrosis (PF) is a disease with high morbidity and mortality rates, but effective treatment options are extremely limited. Mesenchymal stem cells (MSCs) and their derivatives show promise as potential therapeutics for PF. However, the underlying mechanisms responsible for these beneficial effects remain poorly understood. The objective of this study was to elucidate the specific mechanism through which microvesicles derived from human umbilical cord MSCs (MSC-MVs) alleviate PF.</p><p><strong>Methods: </strong>The effects of MSC-MVs on PF in bleomycin (BLM)-induced mice were assessed via histological staining, flow cytometry, and enzyme-linked immunosorbent assays (ELISAs). The potential therapeutic target was identified via RNA sequencing (RNA-seq) analysis, followed by validation via real-time quantitative polymerase chain reaction (RT‒qPCR), ELISAs, scratch testing, and western blotting (WB).</p><p><strong>Results: </strong>MSC-MVs significantly attenuated collagen fiber deposition and downregulated the expression of extracellular matrix components in the lungs of the BLM-induced mice. Moreover, this treatment substantially ameliorated lung inflammation by reducing the monocyte‒macrophage ratio and the TNF-α and IL-6 levels. Further analyses revealed that MSC-MVs inhibited the classic chemotactic CCL2/CCR2 axis of monocyte‒macrophages, leading to reduced recruitment of monocytes‒macrophages to the lungs, which decreased lung inflammation and prevented fibrotic progression. Both in vitro and in vivo findings demonstrated that MSC-MVs suppressed ERK1/2 phosphorylation followed by decreased CCL2 production to modulate monocyte-macrophage migration.</p><p><strong>Conclusions: </strong>Our findings demonstrate that the protective effect of MSC-MVs against BLM-induced lung toxicity was achieved through the inhibition of the ERK1/2 signaling pathway, leading to the suppression of CCL2 expression and subsequent modulation of monocyte-macrophage migration, thereby establishing a theoretical basis for the effect of MSC-MVs in PF.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"145"},"PeriodicalIF":7.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701698","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":"Ferrostatin-1 inhibits tracheal basal cell ferroptosis to facilitate the rapid epithelization of 3D-printed tissue-engineered tracheas.","authors":"Cong Li, Xiaoyang Zhang, Haoqi Cai, Kai Luo, Bozhong Shi, Bo Chen, Guowei Zeng, Jinghao Zheng, Xiaomin He","doi":"10.1186/s13287-025-04263-z","DOIUrl":"10.1186/s13287-025-04263-z","url":null,"abstract":"<p><strong>Background: </strong>Tracheal replacement is a promising approach for treating tracheal defects that are caused by conditions such as stenosis, trauma, or tumors. However, slow postoperative epithelial regeneration often leads to complications, such as infection and granulation tissue formation. Ferroptosis, which is an iron-dependent form of regulated cell death, limits the proliferation of tracheal basal cells (TBCs), which are essential for the epithelialization of tissue-engineered tracheas (TETs). This study explored the potential of ferrostatin-1 (FER-1), which is a ferroptosis inhibitor, to increase TBC proliferation and accelerate the epithelialization of 3D-printed TETs.</p><p><strong>Methods: </strong>TBCs were isolated from rabbit bronchial mucosal tissues and cultured in vitro. Ferroptosis was induced in TBCs at passage 2, as shown by increased reactive oxygen species (ROS) levels, Fe²⁺ accumulation, decreased ATP contents, and mitochondrial damage. TBCs were treated with FER-1 (1 μM) for 48 h to inhibit ferroptosis. The effects on ROS levels, Fe²⁺ levels, ATP contents, and mitochondrial morphology were measured. For in vivo experiments, FER-1-treated TBCs were seeded onto 3D-printed polycaprolactone (PCL) scaffolds, which were implanted into rabbits with tracheal injury. Epithelial regeneration and granulation tissue formation were evaluated 6 months after surgery.</p><p><strong>Results: </strong>FER-1 treatment significantly reduced ferroptosis marker levels in vitro; that is, FER-1 treatment decreased ROS and Fe²⁺ accumulation, ameliorated mitochondrial structures, and increased ATP levels. TBC proliferation and viability were increased after ferroptosis inhibition. In vivo, the group that received 3D-printed scaffolds seeded with TBCs exhibited accelerated TET epithelialization and reduced granulation tissue formation compared with the control groups. These results suggest that inhibiting ferroptosis with FER-1 improves TBC function, leading to more efficient tracheal repair.</p><p><strong>Conclusions: </strong>Ferrostatin-1 effectively inhibits ferroptosis in tracheal basal cells, promoting their viability and proliferation. This results in faster epithelialization of tissue-engineered tracheas, offering a promising strategy for improving tracheal reconstruction outcomes and reducing complications such as infection and granulation tissue formation. Future studies are needed to further investigate the molecular mechanisms underlying ferroptosis in TBCs and its potential clinical applications.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"147"},"PeriodicalIF":7.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701693","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":"Clusterin-mediated polarization of M2 macrophages: a mechanism of temozolomide resistance in glioblastoma stem cells.","authors":"Jianping Wen, Xia Wu, Zhicheng Shu, Dongxu Wu, Zonghua Yin, Minglong Chen, Kun Luo, Kebo Liu, Yulong Shen, Yi Le, Qingxia Shu","doi":"10.1186/s13287-025-04247-z","DOIUrl":"10.1186/s13287-025-04247-z","url":null,"abstract":"<p><p>Glioblastoma remains one of the most lethal malignancies, largely due to its resistance to standard chemotherapy such as temozolomide. This study investigates a novel resistance mechanism involving glioblastoma stem cells (GSCs) and the polarization of M2-type macrophages, mediated by the extracellular vesicle (EV)-based transfer of Clusterin. Using 6-week-old male CD34⁺ humanized huHSC-(M-NSG) mice (NM-NSG-017) and glioblastoma cell lines (T98G and U251), we demonstrated that GSC-derived EVs enriched with Clusterin induce M2 macrophage polarization, thereby enhancing temozolomide resistance in glioblastoma cells. Single-cell and transcriptome sequencing revealed close interactions between GSCs and M2 macrophages, highlighting Clusterin as a key mediator. Our findings indicate that Clusterin-rich EVs from GSCs drive glioblastoma cell proliferation and resistance to temozolomide by modulating macrophage phenotypes. Targeting this pathway could potentially reverse resistance mechanisms, offering a promising therapeutic approach for glioblastoma. This study not only sheds light on a critical pathway underpinning glioblastoma resistance but also lays the groundwork for developing therapies targeting the tumor microenvironment. Our results suggest a paradigm shift in understanding glioblastoma resistance, emphasizing the therapeutic potential of disrupting EV-mediated communication in the tumor microenvironment.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"146"},"PeriodicalIF":7.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701681","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":"Extracellular vesicles derived from mesenchymal stem cells alleviate renal fibrosis via the miR-99b-5p/mTOR/autophagy axis in diabetic kidney disease.","authors":"Rongrong Li, Hongyan Tao, Kai Pan, Rui Li, Zhikun Guo, Xiaoniao Chen, Zongjin Li","doi":"10.1186/s13287-025-04265-x","DOIUrl":"10.1186/s13287-025-04265-x","url":null,"abstract":"<p><strong>Background: </strong>Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) globally, presenting a significant therapeutic challenge. Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) have emerged as promising therapeutic agents. This study explored the therapeutic effects and mechanisms of EVs derived from human placental mesenchymal stem cells (hP-MSCs) on DKD.</p><p><strong>Methods: </strong>EVs were isolated from cultured hP-MSCs and administered to streptozotocin (STZ)-induced diabetic mice and high glucose-treated glomerular mesangial cells. The therapeutic impact of EVs was assessed through histological analysis and biochemical assays. miR-99b-5p expression in EVs and its role in modulating the mechanistic target of rapamycin (mTOR)/autophagy pathway were examined via western blotting and RT‒qPCR.</p><p><strong>Results: </strong>Treatment with hP-MSC-derived EVs significantly alleviated renal fibrosis and improved renal function in DKD models. These EVs were enriched with miR-99b-5p, which targeted and inhibited mTOR signaling, thereby increasing autophagic activity and reducing cellular proliferation and extracellular matrix accumulation in renal tissues.</p><p><strong>Conclusions: </strong>hP-MSC-derived EVs can mitigate renal injury in DKD by modulating the miR-99b-5p/mTOR/autophagy pathway. These findings suggest a potential cell-free therapeutic strategy for managing DKD.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"142"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658701","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":"Airway basal stem cell-derived extracellular vesicles modulate proliferation, migration and collagen deposition of fibroblasts.","authors":"Lisi Luo, Huijie Yang, Junfeng Huang, Difei Chen, Yushan He, Jinsheng Lin, Haikang Zeng, Chu Hua, Zikai Lin, Minting Wu, Yuqin Ma, Qilin Deng, Ming Liu, Shiyue Li","doi":"10.1186/s13287-025-04268-8","DOIUrl":"10.1186/s13287-025-04268-8","url":null,"abstract":"<p><strong>Background: </strong>Human bronchial epithelial cell-derived extracellular vesicles have demonstrated the ability to attenuate fibroblasts activation. However, the specific key effector cell populations mediating this inhibitory effect remain unidentified. Airway basal stem cells (BSCs), which serve as progenitor cells for bronchial epithelial cells, play a critical role in fibrotic remodeling processes and possess significant therapeutic potential. This study aimed to characterize BSC-derived extracellular vesicles (BSC-EVs) and investigate their regulatory influence on fibroblasts behavior.</p><p><strong>Methods: </strong>Airway BSCs were collected through bronchoscopic brushing and differential centrifugation. Fibroblasts were subsequently treated with BSC-EVs at various concentrations to evaluate their dose- and time-dependent effects in vitro. The proteomic composition of BSC-EVs was analyzed using four-dimensional data-independent acquisition quantitative mass spectrometry (4D-DIA). Moreover, a bleomycin-induced pulmonary fibrosis model was established to evaluate the safety and preliminary efficacy of BSC-EVs.</p><p><strong>Results: </strong>We successfully isolated and identified BSC-EVs, which expressed the nucleus-specific marker TP63, indicative of BSCs, but lacked the BSC marker KRT5. Our findings demonstrated that BSC-EVs enhanced fibroblasts proliferation and migration in a dose-dependent manner. Importantly, BSC-EVs significantly attenuated fibroblasts activation and promoted fibroblasts senescence. Utilizing 4D-DIA quantitative proteomics, we revealed that BSC-EVs modulate extracellular matrix remodeling processes and regulate the expression of key proteins, including collagen I/III and matrix metalloproteinases. Animal models utilizing intratracheal administration of BSC-EVs demonstrate efficient reduction of collagen deposition.</p><p><strong>Conclusion: </strong>This study offers an extensive characterization of BSC-EVs, adhering to the guidelines set forth by MISEV2023. The findings underscore the significant therapeutic potential of BSC-EVs in the management of fibrotic diseases.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"140"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658691","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":"Enhancing myelinogenesis through LIN28A rescues impaired cognition in PWMI mice.","authors":"Xuan Wu, Zhechun Hu, Huimin Yue, Chao Wang, Jie Li, Yinxiang Yang, Zuo Luan, Liang Wang, Ying Shen, Yan Gu","doi":"10.1186/s13287-025-04267-9","DOIUrl":"10.1186/s13287-025-04267-9","url":null,"abstract":"<p><strong>Background: </strong>In premature newborn infants, preterm white matter injury (PWMI) causes motor and cognitive disabilities. Accumulating evidence suggests that PWMI may result from defected differentiation of oligodendrocyte precursor cells (OPCs) and impaired maturation of oligodendrocytes. However, the underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>Using RNAscope, we analyzed the expression level of RNA-binding protein LIN28A in individual OPCs. Knockout of one or both alleles of Lin28a in OPCs was achieved by administrating tamoxifen to NG2^CreER::Ai14::Lin28a^flox/+ or NG2^CreER::Ai14::Lin28a^flox/flox mice. Lentivirus expressing FLEX-Lin28a was used in NG2^CreER mice to overexpress LIN28A in OPCs. A series of behavioral tests were performed to assess the cognitive functions of mice. Two-tailed unpaired t-tests was carried out for statistical analysis between groups.</p><p><strong>Results: </strong>We found that the expression of Lin28a was decreased in OPCs in a PWMI mouse model. Knockout of one or both alleles of Lin28a in OPCs postnatally resulted in reduced OPC differentiation, decreased myelinogenesis and impaired cognitive functions. Supplementing LIN28A in OPCs postnatally was able to promote OPC differentiation and enhance myelinogenesis, thus rescuing the cognitive functions in PWMI mice.</p><p><strong>Conclusion: </strong>Our study reveals that LIN28A is critical in regulating postnatal myelinogenesis. Overexpression of LIN28A in OPCs rescues cognitive deficits in PWMI mice by promoting myelinogenesis, thus providing a potential strategy for the treatment of PWMI.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"141"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658694","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":"RNA-binding protein SAMD4A targets FGF2 to regulate cardiomyocyte lineage specification from human embryonic stem cells.","authors":"Na Yi, Han-Rui Wang, Yu-Ping Zhu, Tao Xiao, Qin Lin, Huan Liu, Yi-Lei Meng, Yi-Zhuo Sun, Fang Lin, Sang-Yu Hu, Hua-Ming Cao, Jun-Fang Zhang, Lu-Ying Peng, Li Li","doi":"10.1186/s13287-025-04269-7","DOIUrl":"10.1186/s13287-025-04269-7","url":null,"abstract":"<p><strong>Background: </strong>RNA-binding proteins (RBPs) are essential in cardiac development. However, a large of them have not been characterized during the process.</p><p><strong>Methods: </strong>We applied the human embryonic stem cells (hESCs) differentiated into cardiomyocytes model and constructed SAMD4A-knockdown/overexpression hESCs to investigate the role of SAMD4A in cardiomyocyte lineage specification.</p><p><strong>Results: </strong>SAMD4A, an RBP, exhibits increased expression during early heart development. Suppression of SAMD4A inhibits the proliferation of hESCs, impedes cardiac mesoderm differentiation, and impairs the function of hESC-derived cardiomyocytes. Correspondingly, forced expression of SAMD4A enhances proliferation and promotes cardiomyogenesis. Mechanistically, SAMD4A specifically binds to FGF2 via a specific CNGG/CNGGN motif, stabilizing its mRNA and enhancing translation, thereby upregulating FGF2 expression, which subsequently modulates the AKT signaling pathway and regulates cardiomyocyte lineage differentiation. Additionally, supplementation of FGF2 can rescue the proliferation defect of hESCs in the absence of SAMD4A.</p><p><strong>Conclusions: </strong>Our study demonstrates that SAMD4A orchestrates cardiomyocyte lineage commitment through the post-transcriptional regulation of FGF2 and modulation of AKT signaling. These findings not only underscore the essential role of SAMD4A in cardiac organogenesis, but also provide critical insights into the molecular mechanisms underlying heart development, thereby informing potential therapeutic strategies for congenital heart disease.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"144"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658704","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":"The establishment and regulation of human germ cell lineage.","authors":"Honglin Yu, Ziqi Wang, Jiayue Ma, Ruoming Wang, Shuo Yao, Zhaoyu Gu, Kexin Lin, Jinlan Li, Robert S Young, Ya Yu, You Yu, Min Jin, Di Chen","doi":"10.1186/s13287-025-04171-2","DOIUrl":"10.1186/s13287-025-04171-2","url":null,"abstract":"<p><p>The specification of primordial germ cells (PGCs) during early embryogenesis initiates the development of the germ cell lineage that ensures the perpetuation of genetic and epigenetic information from parents to offspring. Defects in germ cell development may lead to infertility or birth defects. Historically, our understanding of human PGCs (hPGCs) regulation has primarily been derived from studies in mice, given the ethical restrictions and practical limitations of human embryos at the stage of PGC specification. However, recent studies have increasingly highlighted significant mechanistic differences for PGC development in humans and mice. The past decade has witnessed the establishment of human pluripotent stem cell (hPSC)-derived hPGC-like cells (hPGCLCs) as new models for studying hPGC fate specification and differentiation. In this review, we systematically summarize the current hPSC-derived models for hPGCLC induction, and how these studies uncover the regulatory machinery for human germ cell fate specification and differentiation, forming the basis for reconstituting gametogenesis in vitro from hPSCs for clinical applications and disease modeling.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"139"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658707","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":"Exploring the impact of gut microbiota-mediated regulation of exosomal miRNAs from bone marrow mesenchymal stem cells on the regulation of bone metabolism.","authors":"Bin He, Xianglin Shen, Feng Li, Rudan Zhou, Haiyan Xue, Xianqiu Fan, Zhihua Wang, Xinpeng Guo, Yu Fan, Guanghu Luo, Xiujun Zhang, Hongyu Zheng","doi":"10.1186/s13287-025-04256-y","DOIUrl":"10.1186/s13287-025-04256-y","url":null,"abstract":"<p><strong>Background: </strong>Osteoporosis, which is a prevalent metabolic bone disease, is closely associated with imbalances in the gut microbiota.</p><p><strong>Methods: </strong>The ovaries of female 6-month-old Sprague-Dawley rats were surgically removed to induce osteoporosis. Subsequently, 16S rRNA sequencing was employed to characterize the gut microbiota in the osteoporotic rats. Bone marrow mesenchymal stem cells (BMSCs) were isolated from osteoporotic rats and cultured separately, and their osteogenic and adipogenic differentiation was observed. Furthermore, exosomes were extracted from these cells, and miRNA sequencing was performed on the exosomes to identify key miRNAs. Osteoporotic rats were then treated with a member of the gut microbiota, and changes in the osteogenic and adipogenic differentiation of BMSCs were observed.</p><p><strong>Results: </strong>In our investigation, we observed altered proportions of Firmicutes and Bacteroidetes in the guts of ovariectomized rats, which contributed to dysbiosis and subsequent changes in intestinal permeability. The BMSCs exhibited disrupted osteogenic/adipogenic differentiation, which was associated with structural damage to bones. Through the isolation of exosomes from BMSCs and subsequent miRNA analysis, we identified miR-151-3p and miR-23b-3p as potential pivotal regulators of bone metabolism. Furthermore, through 16S rRNA sequencing, we identified g_Ruminococcus and its marked capacity to ameliorate the imbalance in BMSC osteogenic/adipogenic differentiation. Intervention with g_Ruminococcus demonstrated promising outcomes, mitigating bone loss and structural damage to the tibia and femur in ovariectomized rats.</p><p><strong>Conclusions: </strong>These findings highlight the significant role of g_Ruminococcus in alleviating osteoporosis induced by estrogen deficiency, suggesting its therapeutic potential for addressing postmenopausal osteoporosis through the targeted modulation of BMSC-derived exosomal miR-151-3p and miR-23b-3p.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"143"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658698","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":"Reviving hope: unlocking pancreatic islet immortality by optimizing a trehalose-based cryopreservation media and cell-penetrating peptide.","authors":"Zakieh Samsonchi, Roshanak Amirian, Lobat Tayebi, Hossein Derakhshankhah, Zhila Izadi, Ensiyeh Hajizadeh-Saffar","doi":"10.1186/s13287-025-04168-x","DOIUrl":"10.1186/s13287-025-04168-x","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus remains a pervasive global health concern, urging a deeper exploration of islet transplantation as a potential enduring solution. The efficacy of this therapeutic approach pivots on the precision of cryopreservation techniques, ensuring both the viability and accessibility of pancreatic islets. This study delves into the merits of cryopreserving these islets using the disaccharide trehalose, accompanied by an inventive strategy involving poly L proline (PLP) as a cell-penetrating peptide to overcome the cryoprotectant limitations inherent to trehalose.</p><p><strong>Methods: </strong>In our experiments with rat islets, we conducted meticulous viability assessments for fresh and frozen samples. We employed a spectrum of methods, including live/dead staining, insulin/glucagon staining, and measurement of reactive oxygen species (ROS) levels. To gauge functional integrity, we executed glucose-stimulated insulin secretion tests. Subsequently, we transplanted thawed islets into diabetic mice to scrutinize their performance in clinically relevant conditions.</p><p><strong>Results: </strong>Our study yielded compelling results, affirming the successful cryopreservation of pancreatic islets using trehalose and PLP. Viability, as corroborated through live/dead and insulin/glucagon staining, underscored the sustained preservation of frozen islets. Moreover, these preserved islets exhibited functional integrity by releasing insulin responsively to glucose stimulation. Significantly, upon transplantation into diabetic mice, the thawed islets proficiently restored euglycemia, evidenced by a substantial reduction in fasting blood glucose and an enhanced glucose tolerance.</p><p><strong>Conclusion: </strong>Our findings accentuate the potential of trehalose and PLP as sophisticated cryoprotectants for preserving pancreatic islets. Beyond highlighting viability and functionality, the preserved islets demonstrated a remarkable capacity to restore euglycemia post-transplantation. This research holds promise in addressing the inherent limitations of islet transplantation, particularly in the realm of Type 1 diabetes treatment.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"136"},"PeriodicalIF":7.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626171","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}