Stem Cell Research & Therapy最新文献

{"title":"Circ-AARS plays an important role during the odontogenic differentiation of dental pulp stem cells by modulating miR-24-3p/KLF6 expression.","authors":"Meizhi Sui, Jiaxuan Lyu, Jiaxin Zhou, Qian Liao, Zexu Xiao, Mingming Jin, Jiang Tao","doi":"10.1186/s13287-025-04239-z","DOIUrl":"10.1186/s13287-025-04239-z","url":null,"abstract":"<p><strong>Background: </strong>Circular RNAs (circRNAs) play a crucial role in stem cell-based tooth regeneration. However, the functions and underlying mechanisms of circRNAs in tooth regeneration from human dental pulp stem cells (DPSCs) remain largely unclear.</p><p><strong>Methods: </strong>In this study, DPSCs were used for odontogenic differentiation. High-throughput sequencing was performed for differential circRNA analysis. A luciferase reporter assay was conducted to confirm the downstream target of the circRNA, circ-AARS. We then constructed vectors and siRNAs for overexpressing and silencing circ-AARS, miR-24-3p, and Krüppel-like factor 6 (KLF6) and transfected them into DPSCs. Alkaline phosphatase staining, Alizarin Red S staining, western blotting assay, and quantitative reverse transcription-polymerase chain reaction were used to explore the underlying mechanisms of circ-AARS. Finally, a heterotopic bone model was utilized to reveal the regulating effects of circ-AARS.</p><p><strong>Results: </strong>High-throughput sequencing analysis showed that circ-AARS plays an important role during the odontogenic differentiation of DPSCs. Downregulation of circ-AARS inhibited the odontogenic differentiation of DPSCs; however, circ-AARS overexpression promoted their odontogenic differentiation. Bioinformatics analysis and luciferase reporter assay confirmed that both miR-24-3p and KLF6 were the downstream targets of circ-AARS. miR-24-3p downregulation or KLF6 overexpression restored the odontogenic differentiation ability of DPSCs after circ-AARS silencing. KLF6 upregulation restored the odontogenic differentiation ability of DPSCs after KLF6 overexpression. The heterotopic bone model confirmed that circ-AARS overexpression promoted the odontoblastic differentiation of DPSCs.</p><p><strong>Conclusion: </strong>The present study showed that circ-AARS can promote the odontoblastic differentiation of DPSCs by increasing KLF6 expression and sponging miR-24-3p. Taken together, the results indicate that circ-AARS may be a potential positive regulator of odontoblastic differentiation of DPSCs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"137"},"PeriodicalIF":7.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626167","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":"Small extracellular vesicles from young adipose-derived stem cells ameliorate age-related changes in the heart of old mice.","authors":"Jorge Sanz-Ros, Javier Huete-Acevedo, Cristina Mas-Bargues, Nekane Romero-García, Mar Dromant, Michel van Weeghel, Georges E Janssens, Consuelo Borrás","doi":"10.1186/s13287-025-04255-z","DOIUrl":"10.1186/s13287-025-04255-z","url":null,"abstract":"<p><strong>Background: </strong>Aging entails a progressive decline in physiological functions, elevating the risk of age-related diseases like heart failure or aortic stenosis. Stem cell therapies, especially those that use paracrine signaling, can potentially mitigate the adverse effects of aging.</p><p><strong>Objectives: </strong>The objective is to explore the potential of small extracellular vesicles (sEVs) derived from young adipose-derived stem cells (ADSC-sEVs) in reversing structural, molecular, and functional changes associated with aging in the heart.</p><p><strong>Methods: </strong>Aged C57BL/6J mice were treated intravenously with ADSC-sEVs from young mice or PBS as controls. Young mice were included to identify specific age-associated changes. The impact of sEV treatment on cardiac function was assessed using transthoracic echocardiography and physical endurance tests. Histological and molecular analyses were conducted on heart tissue to evaluate structural changes and markers of senescence, inflammation, and oxidative stress. A comprehensive metabolomic analysis was also performed on heart tissues to identify changes in metabolic profiles associated with aging and treatment status.</p><p><strong>Results: </strong>The administration of ADSC-sEVs significantly improves several aging-associated cardiac parameters, including oxidative stress, inflammation, and cellular senescence reductions. We also report on the age-related reversal of myocardial structure and function changes, highlighted by decreased fibrosis and improved vascularization. Notably, echocardiographic assessments reveal that sEV treatments ameliorate diastolic dysfunction and left ventricle structural alterations typically associated with aging. Furthermore, the treatment shifts the heart metabolome towards a more youthful profile.</p><p><strong>Conclusions: </strong>These results denote the potential of ADSC-sEVs as a novel, noninvasive therapeutic strategy for mitigating cardiac aging-associated functional decline.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"138"},"PeriodicalIF":7.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626174","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 cell-derived exosomes and miR-29a-3p mitigate renal fibrosis and vascular rarefaction after renal ischemia reperfusion injury.","authors":"Jing Huang, Lang Shi, Yifei Yang, Fan Zhao, Rengui Chen, Wenliang Liao, Jiefu Zhu, Dingping Yang, Xiongfei Wu, Shangting Han","doi":"10.1186/s13287-025-04226-4","DOIUrl":"10.1186/s13287-025-04226-4","url":null,"abstract":"<p><strong>Background: </strong>Renal fibrosis and vascular rarefaction are significant complications of ischemia/reperfusion (I/R) injury. Human umbilical cord mesenchymal cell-derived exosomes (hucMSC-exos) have shown potential in mitigating these conditions. This study investigates the role of miR-29a-3p in exosomes and its therapeutic effects on I/R-induced renal damage.</p><p><strong>Methods: </strong>Male C57BL/6 mice were subjected to unilateral renal ischemia for 28 min followed by reperfusion. Exosomes and miR-29a-3p mimics/inhibitors were injected into the mice. Renal function, histological analysis, and molecular assays were performed to evaluate fibrosis and vascular integrity.</p><p><strong>Results: </strong>Exosome treatment significantly improved renal function and reduced fibrosis and vascular rarefaction post-I/R. MiR-29a-3p was highly expressed in hucMSC-exos but reduced in renal fibrosis models. MiR-29a-3p mimic reduced, while its inhibitor exacerbated I/R-induced renal fibrosis and vascular rarefaction. Collagen I and TNFR1 were identified as direct targets of miR-29a-3p in fibroblasts and endothelial cells, respectively. Exosomes overexpressing miR-29a-3p provided superior protection compared to unmodified hucMSC-exos.</p><p><strong>Conclusion: </strong>HucMSC-exos, particularly those overexpressing miR-29a-3p, have potent therapeutic effects against renal fibrosis and vascular rarefaction post-I/R. MiR-29a-3p targets TNFR1 and collagen I, highlighting its potential in renal fibrosis therapy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"135"},"PeriodicalIF":7.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617314","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":"Umbilical mesenchymal stem cells mitigate T-cell compartments shift and Th17/Treg imbalance in acute ischemic stroke via mitochondrial transfer.","authors":"Shuna Chen, Chao Han, Zihan Shi, Xin Guan, Liyuan Cheng, Liang Wang, Wei Zou, Jing Liu","doi":"10.1186/s13287-025-04224-6","DOIUrl":"10.1186/s13287-025-04224-6","url":null,"abstract":"<p><strong>Background: </strong>Acute ischemic stroke (AIS) initiates secondary injuries that worsen neurological damage and hinder recovery. While peripheral immune responses play a key role in stroke outcomes, clinical results from immunotherapy have been suboptimal, with limited focus on T-cell dynamics. Umbilical mesenchymal stem cells (UMSCs) offer therapeutic potential due to their immunomodulatory properties. They can regulate immune responses and reduce neuroinflammation, potentially enhancing recovery by fostering a pro-regenerative peripheral immune environment. However, the effect of UMSCs on T-cell dynamics in AIS remains underexplored. This study investigates T-cell dynamics following AIS and examines how UMSCs may mitigate immune dysregulation to develop better treatment strategies.</p><p><strong>Methods: </strong>AIS patients (NIHSS scores 0-15) were recruited within 72 h of stroke onset, with peripheral blood samples collected on Day 0 (enrollment) and Day 7. T-cell compartments were identified by flow cytometry, and plasma cytokine levels were quantified using a cytometric bead array (CBA). Mitochondria in UMSCs were labeled with MitoTracker. Peripheral blood mononuclear cells from patients were isolated, treated with lipopolysaccharide (LPS), and cocultured with UMSCs in both direct contact and Transwell systems. Flow cytometry, CBA, RT-qPCR, and immunofluorescence assays were used to detect T-cell compartments, gene expression markers for helper T (Th) cell differentiation, cytokine profiles, mitochondrial transfer, reactive oxygen species (ROS) production, and mitochondrial membrane potential. Additionally, mitochondrial DNA in UMSCs was depleted. The effects of UMSCs and mitochondria-depleted UMSCs on ischemic stroke mice were compared through behavioral assessments and analysis of the peripheral immune microenvironment.</p><p><strong>Results: </strong>In AIS, T-cell compartments underwent a phenotypic shift from naïve to effector or memory states, with a specific increase in Th17 cells and a decrease in regulatory T cells, leading to alterations in T-cell-mediated immune functions. In an ex vivo co-culture system, LPS stimulation further amplified these disparities, inducing mitochondrial dysfunction and oxidative stress in T cells. Notably, UMSCs restored mitochondrial function and reversed the shift in T-cell compartments through mitochondrial transfer. Critically, UMSC treatment significantly improved both neurological deficits and peripheral immune disorders in ischemic stroke mice, whereas mitochondria-depleted UMSCs failed to produce this effect.</p><p><strong>Conclusions: </strong>Our comprehensive insights into the key attributes of T-cell compartments in acute ischemic stroke and the immune regulatory mechanisms of UMSCs provide a crucial theoretical foundation for understanding peripheral immune disorders in ischemic stroke and the therapeutic potential of UMSC treatment.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"134"},"PeriodicalIF":7.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617316","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":"Enhanced mitochondrial function and delivery from adipose-derived stem cell spheres via the EZH2-H3K27me3-PPARγ pathway for advanced therapy.","authors":"Ming-Min Chang, Dinh Toi Chu, Sheng-Che Lin, Jung-Shun Lee, Thuy Duong Vu, Hue Thi Vu, Thamil Selvee Ramasamy, Shau-Ping Lin, Chia-Ching Wu","doi":"10.1186/s13287-025-04164-1","DOIUrl":"10.1186/s13287-025-04164-1","url":null,"abstract":"<p><strong>Background: </strong>Microenvironmental alterations induce significant genetic and epigenetic changes in stem cells. Mitochondria, essential for regenerative capabilities, provide the necessary energy for stem cell function. However, the specific roles of histone modifications and mitochondrial dynamics in human adipose-derived stem cells (ASCs) during morphological transformations remain poorly understood. In this study, we aim to elucidate the mechanisms by which ASC sphere formation enhances mitochondrial function, delivery, and rescue efficiency.</p><p><strong>Methods: </strong>ASCs were cultured on chitosan nano-deposited surfaces to form 3D spheres. Mitochondrial activity and ATP production were assessed using MitoTracker staining, Seahorse XF analysis, and ATP luminescence assays. Single-cell RNA sequencing, followed by Ingenuity Pathway Analysis (IPA), was conducted to uncover key regulatory pathways, which were validated through molecular techniques. Pathway involvement was confirmed using epigenetic inhibitors or PPARγ-modulating drugs. Mitochondrial structural integrity and delivery efficiency were evaluated after isolation.</p><p><strong>Results: </strong>Chitosan-induced ASC spheres exhibited unique compact mitochondrial morphology, characterized by condensed cristae, enhanced mitochondrial activity, and increased ATP production through oxidative phosphorylation. High expressions of mitochondrial complex I genes and elevated levels of mitochondrial complex proteins were observed without an increase in reactive oxygen species (ROS). Epigenetic modification of H3K27me3 and PPARγ involvement were discovered and confirmed by inhibiting H3K27me3 with the specific EZH2 inhibitor GSK126 and by adding the PPARγ agonist Rosiglitazone (RSG). Isolated mitochondria from ASC spheres showed improved structural stability and delivery efficiency, suppressed the of inflammatory cytokines in LPS- and TNFα-induced inflamed cells, and rescued cells from damage, thereby enhancing function and promoting recovery.</p><p><strong>Conclusion: </strong>Enhancing mitochondrial ATP production via the EZH2-H3K27me3-PPARγ pathway offers an alternative strategy to conventional cell-based therapies. High-functional mitochondria and delivery efficiency show significant potential for regenerative medicine applications.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"129"},"PeriodicalIF":7.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606521","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":"Modeling of lung organoid-based fibrosis for testing the sensitivity of anti-fibrotic drugs.","authors":"Heping Wang, Zhiyi Han, Yang Yang, Lei Liu, Yang Huang, Jiehua Chen, Yulei Wang, Zihao Liu, Lingguo Xin, Yunshan Zhao, Wenjian Wang","doi":"10.1186/s13287-025-04251-3","DOIUrl":"10.1186/s13287-025-04251-3","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary fibrosis models play crucial roles in research of pulmonary fibrosis and anti-fibrosis drug screening. Despite the establishment of several pulmonary fibrosis models including lung fibrosis animals, stem cell differentiation, pulmospheres and so on, the one that mimic the personalized native lung lacks.</p><p><strong>Methods: </strong>We here developed a lung organoid-based fibrosis (LOF) model from native lung tissue, and the potential of the LOFs for the sensitivity test of anti-fibrotic drugs was evaluated.</p><p><strong>Results: </strong>Our results showed that the LOFs could be self-organized from the lung organoids and the fibroblasts derived from native lung tissue. Histochemical examination demonstrated that the LOFs were characteristic of pulmonary fibrosis in structure. Single-cell sequencing (SCS) further revealed that the cell clusters mimicked fibrotic process at cellular and molecular levels in the LOFs. Drug sensitivity test indicated that the LOFs could not only be used to evaluate the efficacy of anti-fibrotic drugs, but also display their toxicity.</p><p><strong>Conclusions: </strong>We demonstrate that the LOFs represent an efficient fibrotic model that mimics faithfully the personalized characteristics of native lung tissue.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"132"},"PeriodicalIF":7.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606526","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":"Hormone correction of dysfunctional metabolic gene expression in stem cell-derived liver tissue.","authors":"Alvile Kasarinaite, Maria Jimenez Ramos, Mariana Beltran-Sierra, Elena F Sutherland, Pedro Arede Rei, Make Zhao, Ying Chi, Meryam Beniazza, Andrea Corsinotti, Timothy J Kendall, Neil C Henderson, Jonathan A Fallowfield, Philippa T K Saunders, David C Hay","doi":"10.1186/s13287-025-04238-0","DOIUrl":"10.1186/s13287-025-04238-0","url":null,"abstract":"<p><p>The increase in metabolic dysfunction-associated steatotic liver disease (MASLD) and its progression to metabolic dysfunction-associated steatohepatitis (MASH) is a worldwide healthcare challenge. Heterogeneity between men and women in the prevalence and mechanisms of MASLD and MASH is related to differential sex hormone signalling within the liver, and declining hormone levels during aging. In this study we used biochemically characterised pluripotent stem cell derived 3D liver spheres to model the protective effects of testosterone and estrogen signalling on metabolic liver disease 'in the dish'. We identified sex steroid-dependent changes in gene expression which were protective against metabolic dysfunction, fibrosis, and advanced cirrhosis patterns of gene expression, providing new insight into the pathogenesis of MASLD and MASH, and highlighting new druggable targets. Additionally, we highlight gene targets for which drugs already exist for future translational studies.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"130"},"PeriodicalIF":7.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606524","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":"Adipose stromal cells increase insulin sensitivity and decrease liver gluconeogenesis in a mouse model of type 1 diabetes mellitus.","authors":"Hsiao-Chi Lai, Yen-Ju Lee, Pei-Hsuan Chen, Chia-Hua Tang, Lee-Wei Chen","doi":"10.1186/s13287-025-04225-5","DOIUrl":"10.1186/s13287-025-04225-5","url":null,"abstract":"<p><strong>Background: </strong>Diabetic ketoacidosis (DKA) is a serious complication of hyperglycemic emergency caused by insulin deficiency through accelerated liver gluconeogenesis and glycogenolysis. DKA is most common in type 1 diabetes (T1D). Transplantation of islet cells and pancreas is an alternative to insulin injection for treating T1D. However, this alternative is only suitable for some patients. This study investigated the effects and mechanisms of adipose stromal vascular fraction (SVF) cells on liver gluconeogenesis and insulin sensitivity in an insulin-dependent T1D animal model.</p><p><strong>Methods: </strong>SVF cells were obtained from wild-type inguinal adipose tissue and transplanted into the peritoneal cavity of type I diabetic Akita (Ins2^Akita) mice.</p><p><strong>Results: </strong>We found that transplantation of 5 × 10⁶ SVF cells from wild-type adipose tissue significantly downregulated proinflammatory genes of TNF-α, IL-1β, IL-33, iNOS, and DPP4 in the liver and upregulated anti-inflammatory factors IL-10 and FOXP3 in blood serum and liver tissue 7 days after injection. Moreover, we found that the expression levels of G6pc and Pck1 were significantly decreased in the Akita mice livers. Furthermore, the intraperitoneal insulin tolerance test assay showed that diabetic Akita mice significantly had increased insulin sensitivity, reduced fasting blood glucose, and restored glucose-responsive C-peptide expression compared with the control Akita group. This result was noted 14 days after administration of 5 × 10⁶ or 1 × 10⁷ SVF cells from wild-type adipose tissue into diabetic Akita mice.</p><p><strong>Conclusions: </strong>Together, these findings suggest that adipose tissue-derived SVF cells could suppress liver inflammation, regulate liver gluconeogenesis, and improve insulin sensitivity in an animal model with T1D. Therefore, adipose SVF cells may be novel cellular therapeutic alternatives to maintain steady liver gluconeogenesis in T1D.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"133"},"PeriodicalIF":7.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606506","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":"Hepatic progenitor cells reprogrammed from mouse fibroblasts repopulate hepatocytes in Wilson's disease mice.","authors":"Kai Liu, Li Li, Yu He, Song Zhang, Hong You, Ping Wang","doi":"10.1186/s13287-025-04253-1","DOIUrl":"10.1186/s13287-025-04253-1","url":null,"abstract":"<p><strong>Background: </strong>Wilson's disease (WD) is a genetic disorder that impairs the excretion of copper in hepatocytes and results in excessive copper deposition in multiple organs. The replacement of disordered hepatocytes with functional hepatocytes can serve as a lifelong therapeutic strategy for the treatment of WD. The aim of this study was to determine the hepatocyte repopulation effects of fibroblast-derived hepatic progenitor cells in the treatment of WD.</p><p><strong>Methods: </strong>Induced hepatic progenitor cells (iHPCs) were generated through direct reprogramming of adult mouse fibroblasts infected with lentivirus carrying both the Foxa3 and Hnf4α genes. These iHPCs were subsequently identified and transplanted into copper-overload WD mice with the Atp7b (H1071Q) mutation via caudal vein injection.</p><p><strong>Results: </strong>After lentivirus infection, the fibroblasts transformed into Foxa3- and Hnf4α-overexpressing cobblestone-like cells with reduced expression of fibroblast markers and increased expression of epithelial cell and hepatic progenitor cell markers, i.e., iHPCs. Sixteen weeks after transplantation into WD mice, approximately 2% of hepatocytes were derived from iHPCs, and these iHPC-derived hepatocytes expressed a tight junction-associated protein of the bile canal, tight junction protein 1 (Zo1). There was a decrease in the serum copper concentration and relative activity of serum ceruloplasmin at weeks 4 and 8 after iHPCs transplantation compared with those of WD fed mice administered saline or fibroblasts. Furthermore, iHPC transplantation markedly reduced the proportion of CD8⁺ T lymphocytes and natural killer cells compared with those in fibroblast-transplanted WD mice and downregulated the transcription of the inflammatory cytokines, including tumor necrosis factor α (Tnfα), interleukin 1β (IL-1β), and IL-6, compared with those in WD mice and in fibroblast-transplanted WD mice.</p><p><strong>Conclusion: </strong>iHPCs reprogrammed from adult fibroblasts can repopulate hepatocytes and exert therapeutic effects in WD mice, representing a potential replacement therapy for clinical application.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"131"},"PeriodicalIF":7.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606522","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":"Improvement in long-term survival with mesenchymal stem cell transplantation in systemic sclerosis patients: a propensity score-matched cohort study.","authors":"Wenyi Yuan, Mian Liu, Dapeng Yang, Yirui Shi, Zhikang Wang, Xuan Cao, Jun Liang, Linyu Geng, Huayong Zhang, Xuebing Feng, Ziyi Jin, Dandan Wang, Lingyun Sun","doi":"10.1186/s13287-025-04237-1","DOIUrl":"10.1186/s13287-025-04237-1","url":null,"abstract":"<p><strong>Background: </strong>The intricate and varied clinical presentations of systemic sclerosis (SSc) pose significant challenges for treatment. While several studies have investigated the therapeutic potential of mesenchymal stem cell transplantation (MSCT), the clarity of its long-term outcomes for SSc patients is still lacking.</p><p><strong>Methods: </strong>Data on MSCT were extracted from the medical records of inpatients at Nanjing Drum Tower Hospital between January 2013 and December 2022. Additionally, Baseline characteristics and survival outcomes were ascertained from medical records and telephone follow-up. Propensity score matching (PSM) was employed to equalize the baseline characteristics of the patient groups, while survival analysis and multivariate Cox regression assessed the relationship between received MSCT and all-cause mortality and disease-specific survival rates in SSc patients.</p><p><strong>Results: </strong>Of the 333 hospitalized SSc patients, 113 patients underwent MSCT. The log-rank test revealed significantly higher survival rates in the MSCT group compared to the control group (10-year survival rate 89.4% vs. 73.4%, P = 0.002). In the PSM cohort, receiving MSCT significantly reduced mortality (10-year survival 88.0% vs. 79.9%, P = 0.032). Multivariate Cox regression analysis indicated that MSCT was linked to a reduced mortality risk during the follow-up period (HR 0.38, 95% CI 0.19-0.75, P = 0.005). This finding was further confirmed in the matched cohort (HR 0.38, 95% CI 0.18-0.82, P = 0.014). Subgroup analyses revealed that treated with MSCT was correlated with reduced mortality in patients of various demographics, including younger age at diagnosis (≤ 47 years), female, diffuse cutaneous systemic sclerosis (dcSSc) subtype, concurrent arthritis, pulmonary arterial hypertension (PAH), and interstitial lung disease (ILD).</p><p><strong>Conclusion: </strong>MSCT significantly enhances the survival rate of patients with SSc, with outcomes related to the age at diagnosis. MSCT is particularly indicated for patients with comorbid conditions, including PAH, ILD, digital ulcers, and arthritis, as well as those with severe disease presentations associated with the dcSSc subtype.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"128"},"PeriodicalIF":7.1,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586724","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}