Stem Cell Research & Therapy最新文献

{"title":"Autoimmunity and clinical pathology amelioration in SLE by dexamethasone primed mesenchymal stem cell derived conditioned media.","authors":"Khushbu Priya, Sonali Rawat, Doli Das, Manaswi Chaubey, Hiral Thacker, Kiran Giri, Shambhavi Singh, Madhukar Rai, Sujata Mohanty, Geeta Rai","doi":"10.1186/s13287-025-04208-6","DOIUrl":"10.1186/s13287-025-04208-6","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the therapeutic potential of cell-free Dexamethasone (Dex) primed Wharton's jelly Mesenchymal stem cells derived conditioned media (DW) in addressing complications associated with systemic lupus erythematosus (SLE), focusing on its immunomodulatory effects.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells from 74 SLE patients were stimulated and treated with Dex, DW and W. Culture supernatant were evaluated for autoantibody levels, IL-10 and TGF-β by ELISA, Treg subtypes, Breg subtypes, TH17 cells Double negative T cells and inflammatory neutrophils by flow cytometry, IL-10 and IL-17A by qPCR. In vivo studies were performed on 60 pristane induced female BALB/c mice. Dex and DW treatments were evaluated for autoantibody production, proteinuria, immunomodulation of immune cells, organ function, and histopathology. In vivo imaging of internal organs was done using VevoLAZR-X photoacoustic imaging system.</p><p><strong>Results: </strong>DW treatment significantly expanded different Treg and Bregs subtypes. DW suppressed pathogenic TH17, Double negative T cells and inflammatory neutrophils. Comparative analyses with hydroxychloroquine showed similar effects, with combined treatment enhancing efficacy. Inhibition studies implicated the TGF-β pathway in DW's mechanism. In vivo studies using the PIL mouse model showed that DW treatment reduced mortality, prevented proteinuria, and ameliorated symptoms such as limb inflammation, seizures, and alopecia. Detailed organ-specific evaluations through live imaging and histopathological analyses revealed DW's protective effects on kidneys, liver, lungs, heart, and spleen.</p><p><strong>Conclusion: </strong>DW shows promise as a cell-free biological therapy for SLE and related autoimmune disorders, capable of modulating immune responses effectively without the adverse effects of glucocorticoids.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"158"},"PeriodicalIF":7.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744024","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 mutual impacts of stem cells and sleep: opportunities for improved stem cell therapy.","authors":"Sharif Moradi, Masoumeh Nouri, Mohammad-Taher Moradi, Reza Khodarahmi, Morteza Zarrabi, Habibolah Khazaie","doi":"10.1186/s13287-025-04235-3","DOIUrl":"10.1186/s13287-025-04235-3","url":null,"abstract":"<p><p>Sleep is an indispensable physiological function regulated by circadian rhythms, which influence the biological pathways and overall health of the body. Sleep is crucial for the maintenance and restoration of bodily systems, and disturbances can lead to various sleep disorders, which can impair both mental and physical health. Treatment options for these disorders encompass lifestyle modifications, psychotherapy, medications, and therapies such as light therapy and surgery. Not only sleep deprivation has a significant impact on essential organs, but it also influences various types of stem cells in the body. In this review, we explore the connection between sleep and various types of stem cells, highlighting how circadian rhythms regulate stem cell activities that are vital for tissue regeneration and homeostasis. Disruptions in sleep can hinder stem cell self-renewal, homing, proliferation, function, and differentiation, thereby affecting tissue regeneration and overall health. We also discuss how transplantation of stem cells and their products may help improve sleep disorders, how sleep quality affects stem cell behavior, and the implications for stem cell therapies. Notably, while certain stem cell transplantations can disrupt sleep, enhancing sleep quality may improve the efficacy of these therapies. Finally, stem cells can be utilized to model sleep disorders, offering valuable insights into their underlying mechanisms.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"157"},"PeriodicalIF":7.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744032","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":"Examining the effect of intermittent cycling throughout a 3-h period on peripheral blood concentrations of haemopoietic stem and progenitor cells and cytolytic natural killer cells.","authors":"Phoebe A Cox, Fendi Pradana, Ella Noble, Samuel J E Lucas, Guy Pratt, Mark T Drayson, Kevin Amin, Francesca A M Kinsella, Alex J Wadley","doi":"10.1186/s13287-025-04261-1","DOIUrl":"https://doi.org/10.1186/s13287-025-04261-1","url":null,"abstract":"<p><strong>Background: </strong>Peripheral blood stem cell (PBSC) donation is the primary procedure used to collect haemopoietic stem and progenitor cells (HSPCs) for haemopoietic stem cell transplants (HSCT), however there is a clinical need to reduce collection times and achieve sufficient HSPC doses for successful engraftment. Short bouts of interval cycling transiently enrich peripheral blood with HSPCs and cytolytic natural killer (CD56^dim NK) cells, which predict engraftment success and prevent post-transplant complications respectively. Despite this, feasible protocols for use during PBSC collections (≈ 3 h) have yet to be evaluated.</p><p><strong>Methods: </strong>In a randomised crossover design, 18 adults (9 young: 22.7 ± 3.2 years, 9 older: 65.2 ± 12.9 years) completed 3 × 3-h trials: high-intensity interval exercise (HIIE, 9 × 2-min cycling at 80-85% heart rate (HR)max/9 × 18 min rest), moderate-intensity interval exercise (MIIE, 9 × 4-min cycling at 65-70% HRmax/9 × 16 min rest) and REST (180 min). Immune cell subsets, including HSPCs and CD56^dim NK concentrations (cells/µL) were determined across 18 timepoints and area under the curve (AUC, cells/µL x minutes) and total cell dose (cells/kg) were estimated.</p><p><strong>Results: </strong>By design, MIIE elicited lower average and peak HR and rating of perceived exertion than HIIE and was reported as more enjoyable. All cell subset concentrations increased following each interval of MIIE and HIIE. Across all participants, the estimated cell dose of total lymphocytes, monocytes, T cells, CD56^bright and CD56^dim NK was greater in MIIE and HIIE versus REST (p < 0.03), but there were no differences between MIIE and HIIE. The magnitude of change versus REST was greatest for CD56^dim NK versus all cell subsets, and AUC was significantly greater in HIIE versus REST for this cell type only (p < 0.0001). There were no statistically significant differences in HSPC AUC (p = 0.77) or cell dose (p = 0.0732) in MIIE and HIIE versus REST. Age did not predict any changes across trials or timepoints for any cell type.</p><p><strong>Conclusion: </strong>Persistent mobilisation of peripheral blood immune cells throughout 3 h of MIIE and HIIE evoked sustained numbers of CD56^dim NK cells, but there was no reliable difference in HSPCs compared to a time-matched period of rest.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"155"},"PeriodicalIF":7.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744030","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":"Biological characteristics and transcriptomic profile of adipose-derived mesenchymal stem cells isolated from prion-infected murine model.","authors":"Mohammed Zayed, Yong-Chan Kim, Byung-Hoon Jeong","doi":"10.1186/s13287-025-04273-x","DOIUrl":"https://doi.org/10.1186/s13287-025-04273-x","url":null,"abstract":"<p><strong>Background: </strong>Prion diseases are characterized by accumulation of misfolded host prion proteins (PrP^Sc) that produce aggregates in brain tissue. Mesenchymal stem cells (MSCs) have been identified as potential therapeutic candidates for prion diseases. However, it has been demonstrated that MSCs maintained and expressed PrP^Sc levels following inoculation, raising concerns regarding their safe and effective use in medical applications. Prion infectivity has been reported in fat tissues, thus the response of adipose-derived MSCs (AdMSCs) to prion infection needs to be fully studied.</p><p><strong>Methods: </strong>For this study, we analyzed the properties of AdMSCs isolated from mice infected with the ME7 scrapie strain and compared them with negative controls. We investigated morphology, viability, immunophenotyping, markers of inflammation, migration activity, and neurotrophic factors. RNA sequencing (RNA-Seq) was performed to identify transcriptome profile changes.</p><p><strong>Results: </strong>AdMSCs derived from ME7-infected mice displayed immunophenotypes similar to cells from negative controls, but they were larger with lower viability (p < 0.05). ME7 infection caused higher expression of inflammatory mediators CCL5, TNF-α, C3, and IL6 (p < 0.05 and p < 0.01) and low expression of the stem cell marker, CXCR4 (p < 0.05) which was confirmed by immunofluorescence staining. The results showed decreased migration activity and wound closure ability of AdMSCs isolated from ME7-infected mice as confirmed by Transwell migration and scratch wound assays (p < 0.05 and p < 0.001), respectively. The RNA-Seq results detected 367 differentially expressed genes between AdMSCs from ME7-infected mice and those from the negative controls, and negative regulation of locomotion, extracellular matrix (ECM) organization, collagen-containing ECM, and extracellular structure organization genes were common in AdMSCs from ME7-infected mice. Transcriptomic analysis revealed that pathways enriched in AdMSCs from ME7-infected mice included those involved in the PI3K-Akt signaling pathway, cell adhesion, protein digestion and absorption, and cytokine-cytokine receptor interactions. Interestingly, genes related to the regulation of iron storage, such as Hp and hepcidin, were upregulated in AdMSCs isolated from ME7-infected mice.</p><p><strong>Conclusions: </strong>Based on these data, therapeutic strategies for AdMSCs in prion disease should be further investigated.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"154"},"PeriodicalIF":7.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744026","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":"Amniotic fluid-derived mesenchymal stem cells as a therapeutic tool against cytokine storm: a comparison with umbilical cord counterparts.","authors":"Salvatore Vaiasicca, David W James, Gianmarco Melone, Omar Saeed, Lewis W Francis, Bruna Corradetti","doi":"10.1186/s13287-025-04262-0","DOIUrl":"https://doi.org/10.1186/s13287-025-04262-0","url":null,"abstract":"<p><strong>Background: </strong>Several immunosuppressive therapies have been proposed as key treatment options for critically ill patients since the first appearance of severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) from different sources have been considered for their potential to attenuate the cytokine storm associated to COVID-19 and the consequent multi-organ failure, providing evidence for safe and efficacious treatments. Among them, administration of umbilical cord-derived MSCs (UC-MSCs) has demonstrated a significant increase in survival rates, largely due to their potent immunosuppressive properties.</p><p><strong>Methods: </strong>We applied next-generation sequencing (NGS) analysis to compare the transcriptomic profiles of MSCs isolated from two gestational sources: amniotic fluid (AF) obtained during prenatal diagnosis and their clinically relevant umbilical cord counterparts, for which datasets were publicly available. A full meta-analysis was performed to identify suitable GEO and NGS datasets for comparison between AF- and UC-MSC samples.</p><p><strong>Results: </strong>Transcriptome analysis revelaed significant differences between groups, despite both cell lines being strongly involved in the tissue development, crucial to achieve the complex task of wound healing. Significantly enriched hallmark genes suggest AF-MSC superior immunomodulatory features against signaling pathways actively involved in the cytokine storm (i.e., IL-2/STAT, TNF-a/NFkB, IL-2/STAT5, PI3K/AKT/mTOR).</p><p><strong>Conclusions: </strong>The data presented here suggest that AF-MSCs hold significant promise for treating not only COVID-19-associated cytokine storms but also a variety of other inflammatory syndromes (i.e., those induced by bacterial infections, autoimmune disorders, and therapeutic interventions). Realizing the full potential of AF-MSCs as a comprehensive therapeutic approach in inflammatory disease management will require more extensive clinical trials and in-depth mechanistic studies.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"151"},"PeriodicalIF":7.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744022","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":"3D culturing as a promising strategy to enhance the angiogenic potential of adipose stem cell-derived secretome: insights into the role of miR-145-5p/ANGPT2 axis.","authors":"G Gerini, E Mari, P Pontecorvi, S Camero, E Romano, D Ranieri, F Megiorni, P Fioramonti, A Angeloni, C Marchese, S Ceccarelli","doi":"10.1186/s13287-025-04277-7","DOIUrl":"https://doi.org/10.1186/s13287-025-04277-7","url":null,"abstract":"<p><strong>Background: </strong>Adipose-derived mesenchymal stem cells (ASCs) represent a valid therapeutic option for clinical application in several diseases, mostly due to the paracrine activity of their secretome, exerting pro-angiogenic, antinflammatory and immunosuppressive effects. Recently, 3D culturing models has been shown to significantly influence the intrinsic characteristics of these cells, their gene expression and the secretome's composition, thus affecting ASC paracrine effects and clinical potential. This study aims to investigate the feasibility of exploiting 3D culturing as a tool to improve ASC secretome therapeutic efficacy.</p><p><strong>Methods: </strong>ASCs were cultured in monolayers via conventional two-dimensional (2D) methods or induced to form 3D spheroids by seeding them on 96-well ultra-low attachment (ULA) plates. The phenotypical characterization of 3D-ASCs was performed through immunofluorescence analyses. The composition and angiogenic potential of 3D-ASC-derived secretome was assessed by means of protein array and functional tube formation assay, respectively. We analyzed the expression profile of 92 angiogenesis-related genes in 2D versus 3D cultures through a qRT-PCR array, and GO term enrichment analysis followed by network analysis was applied to identify the top hub genes. The expression of specific angiomiRs in 3D-ASCs and their secretome was assessed by qRT-PCR. The role of miR-145-5p was investigated through transfection with specific mimics/anti-miR.</p><p><strong>Results: </strong>3D-ASCs showed increased stemness, cell-cell and cell-ECM interactions with respect to 2D-cultured cells. 3D culturing increased the secretion of cytokines involved in the promotion of angiogenesis, resulting in improved angiogenic effects on HUVEC cells. Mechanistically, qRT-PCR array data indicated downregulation of angiopoietin-2 (ANGPT2) as a key factor in the 3D-ASC-secretome-induced angiogenesis. In addition, ANGPT2 was recognized as a predicted target of miR-145-5p, one of the angiomiRs found upregulated in 3D-ASCs. Depletion of miR-145-5p significantly altered ASC secretome angiogenic potential and ANGPT2 expression on HUVEC cells.</p><p><strong>Conclusions: </strong>All these findings corroborate our hypothesis that 3D culturing is able to positively modulate ASC gene expression and secretome composition in terms of pro-angiogenic potential. Indeed, our study contributes to shed light on the role of the miR-145-5p/ANGPT2 axis in this process, opening the way to innovative potentiation strategies to implement secretome-based therapies, with broad clinical applications.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"153"},"PeriodicalIF":7.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744020","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":"Efficacy of mesenchymal stem cell-based therapies in the treatment of perianal fistulizing Crohn's disease: a systematic review and meta-analysis.","authors":"Lucas Guillo, Robinson Gravier Dumonceau, Mélanie Vélier, Mélanie Serrero, Fanny Grimaud, Florence Sabatier, Jérémy Magalon","doi":"10.1186/s13287-025-04272-y","DOIUrl":"https://doi.org/10.1186/s13287-025-04272-y","url":null,"abstract":"<p><strong>Background: </strong>Perianal lesions of Crohn's disease (CD) are complex and disabling conditions. Mesenchymal stem cell (MSC)-based therapies have emerged as an innovative approach in managing refractory perianal fistulizing CD. We conducted a systematic review and meta-analysis to describe and compare combined remission and clinical outcomes of MSC-based therapies, and then whether one approach stands out from the rest.</p><p><strong>Methods: </strong>We searched in MEDLINE, EMBASE and CENTRAL (up to December 31, 2023) all prospective studies assessing a local injection of MSC-based therapy in perianal fistulas of CD. The primary outcome was achievement of combined remission. MSC-based therapy strategies were compared.</p><p><strong>Results: </strong>Twenty-five studies were included in the meta-analysis, enrolling 596 patients with perianal fistulizing CD. The combined remission rate at 3, 6 and 12 months were 36.2% (95% confidence interval (CI), 24.5-49.7), 57.9% (95% CI 51.3-64.2) and 52% (95% CI 38.8-64.8), respectively. MSC-based therapies demonstrated a significant effect in achieving combined remission compared to placebo at 3 months (relative risk (RR) = 1.6; 95% CI 1.0-2.8) and at 6 months (RR = 1.5; 95% CI 1.1-1.9). At 6 months, the combined remission rate was 57.2% (95% CI 47.2-66.6) for adipose-derived stem cells (ASCs) and 55.7% (95% CI 26.4-81.5) for bone marrow-derived stem cells (BMSCs). In the network meta-analysis, allogeneic ASCs and BMSCs did not demonstrate superiority over each other (RR = 0.74; 95% CI 0.31-1.77).</p><p><strong>Conclusion: </strong>MSC-based therapies are effective for achieving combined remission of refractory and/or complex perianal fistulizing CD. The optimal efficacy effect is reached after 6 months of treatment. No superiority has yet been demonstrated between ASCs and BMSCs therapies.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"152"},"PeriodicalIF":7.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744028","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":"From gut to liver: organoids as platforms for next-generation toxicology assessment vehicles for xenobiotics.","authors":"Sulaiman Mohammed Alnasser","doi":"10.1186/s13287-025-04264-y","DOIUrl":"10.1186/s13287-025-04264-y","url":null,"abstract":"<p><p>Traditional toxicological assessment relied heavily on 2D cell cultures and animal models of study, which were inadequate for the precise prediction of human response to chemicals. Researchers have now shifted focus on organoids for toxicological assessment. Organoids are 3D structures produced from stem cells that mimic the shape and functionality of human organs and have a number of advantages compared to traditional models of study. They have the capacity to replicate the intricate cellular microenvironment and in vivo interactions. They offer a physiologically pertinent platform that is useful for the researchers to monitor cellular responses in a more realistic manner and evaluate drug toxicity. Additionally, organoids can be created from cells unique to a patient, allowing for individualized toxicological research and providing understanding of the inter-individual heterogeneity in drug responses. Recent developments in the use of gut and liver organoids for assessment of the xenobiotics (environmental toxins and drugs) is reviewed in this article. Gut organoids can reveal potential damage to the digestive system and how xenobiotics affect nutrient absorption and barrier function. Liver is the primary site of detoxification and metabolism of xenobiotics, usually routed from the gut. Hence, these are linked and crucial for evaluating chemical or pollutant induced organ toxicity, forecasting their metabolism and pharmacokinetics. When incorporated into the drug development process, organoid models have the potential to improve the accuracy and efficiency of drug safety assessments, leading to safer and more effective treatments. We also discuss the limitations of using organoid-based toxicological assays, and future prospects, including the need for standardized protocols for overcoming reproducibility issues.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"150"},"PeriodicalIF":7.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes derived from a mesenchymal-like endometrial regenerative cells ameliorate renal ischemia reperfusion injury through delivery of CD73.","authors":"Bo Shao, Hong-da Wang, Shao-Hua Ren, Qiang Chen, Zhao-Bo Wang, Yi-Ni Xu, Tong Liu, Cheng-Lu Sun, Yi-Yi Xiao, Hong-Yu Jiang, Yi-Cheng Li, Peng-Yu Zhao, Guang-Mei Yang, Xu Liu, Yu-Fan Ren, Hao Wang","doi":"10.1186/s13287-025-04275-9","DOIUrl":"10.1186/s13287-025-04275-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Renal ischemia reperfusion (I/R) injury is a major contributor to graft dysfunction and inflammation leading to graft loss. The deregulation of purinergic signaling has been implicated in the pathogenesis of renal I/R injury. CD73 and the generation of adenosine during purine metabolism to protect against renal I/R injury. A mesenchymal-like endometrial regenerative cell (ERC) has demonstrated a significant therapeutic effect on renal I/R injury. CD73 is a phenotypic marker of human endometrial regenerative cell exosomes (ERC-Exo). However, its immunosuppressive function in regulating purinergic metabolism has been largely neglected. Here, we investigate the protective effects and mechanism of ERC-Exo against renal I/R injury.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Lentivirus-mediated CRISPR-Cas9 technology was employed to obtain CD73-specific knockout ERC-Exo (CD73&lt;sup&gt;-/-&lt;/sup&gt;ERC-Exo). C57BL/6 mice who underwent unilateral ureteral obstruction were divided into the Untreated, ERC-Exo-treated, and CD73&lt;sup&gt;-/-&lt;/sup&gt;ERC-Exo-treated groups. Renal function and pathological injury were assessed 3 days after renal reperfusion. The infiltration of CD4&lt;sup&gt;+&lt;/sup&gt; T cells and macrophages was analyzed by flow cytometry and immunofluorescence staining in kidneys. CD73-mediated immunosuppressive activity of ERC-Exo was investigated by bone marrow-derived macrophages (BMDM) co-culture assay in vitro. Flow cytometry determined macrophage polarization. ELISA and Treg proliferation assays detected the function of macrophages. Furthermore, the role of the MAPK pathway in CD73-positive Exo-induced macrophage polarization was also elucidated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with Untreated and CD73&lt;sup&gt;-/-&lt;/sup&gt;ERC-Exo-treated groups, CD73-positive Exo effectively improved the serum creatinine (sCr), blood urea nitrogen (BUN), and necrosis and detachment of tubular epithelial cells, necrosis and proteinaceous casts induced by ischemia. CD73 improved the capacity of ERC-Exo on CD4&lt;sup&gt;+&lt;/sup&gt; T cell differentiation in the renal immune microenvironment. Surprisingly, ERC-Exosomal CD73 significantly decreased the populations of M1 cells but increased the proportions of M2 in kidneys. Furthermore, CD73-positive Exo markedly reduced the levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and increased anti-inflammatory factors (IL-10) level in kidneys. ERC-Exosomal CD73 improved macrophage immunoregulatory function associated with the MAPK pathway (including ERK1/2 and p38 pathways), which exerted a potent therapeutic effect against renal I/R.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;These data collected insight into how ERC-Exo facilitated the hydrolysis of proinflammatory ATP to immunosuppressive ADO via CD73. CD73 is a critical modulator of the MAPK signaling pathway, inducing a polarization shift of macrophages towards an anti-inflammatory phenotype. This study highlights the significance of ERC-Exosomal CD73 in contributing ","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"148"},"PeriodicalIF":7.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721537","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":"LincRNA-ASAO promotes dental pulp repair through interacting with PTBP1 to increase ALPL alternative splicing.","authors":"Fuchun Fang, Xiaolan Guo, Sitong Liu, Longrui Dang, Zehao Chen, Yumeng Yang, Lu Chen, Jiahao Lin, Wei Qiu, Zhao Chen, Buling Wu","doi":"10.1186/s13287-025-04274-w","DOIUrl":"10.1186/s13287-025-04274-w","url":null,"abstract":"<p><strong>Background: </strong>Alternative splicing not only expands the genetic encoding of genes but also determines cellular activities. This study aimed to elucidate the regulation mechanism and biological functions of lincRNA-ASAO in the process of odontogenesis-related genes alternative splicing mediated odontogenic differentiation of hDPSCs.</p><p><strong>Methods: </strong>RACE, RNA-seq, FISH and bioinformatics techniques were used to identify novel lincRNA-ASAO. ALP staining, alizarin red staining, qRT-PCR and western blot were used to identify the role of lincRNA-ASAO in regulating the odontoblast differentiation of hDPSCs. The binding protein PTBP1 of lincRNA-ASAO was screened by RNA-Pulldown, protein profiling and bioinformatics. The target gene ALPL of lincRNA-ASAO/PTBP1 was identified by RNA-seq, bioinformatics technology and DNA agarose gel electrophoresis. FISH, IF, PAR-CLIP and bioinformatics techniques were used to determine the roles of lincRNA-ASAO, PTBP1 and ALPL pre-mRNA in the odontoblast differentiation of hDPSCs.</p><p><strong>Results: </strong>We identified a novel lincRNA-ASAO that could promote the odontogenic differentiation of human Dental Pulp Stem Cells (hDPSCs). And, the interaction between lincRNA-ASAO and alternative splicing factor PTBP1 promoted the odontoblast differentiation of hDPSCs. In addition, lincRNA-ASAO forms duplexes with ALPL pre-mRNA, targeting PTBP1 to exonic splicing silencer (ESS) of ALPL and regulating exon 2 skipping. Notably, lincRNA-ASAO/PTBP1 regulated ALPL production to increase the type 2 splice variant, which promoted the odontoblast differentiation of hDPSCs.</p><p><strong>Conclusions: </strong>We have identified the novel lincRNA-ASAO, which can promote the odontoblast differentiation of hDPSCs. The mechanism study found that lincRNA-ASAO/PTBP1 mediated the exon 2 skipping of ALPL pre-mRNA, resulting in the type 2 splice variant of ALPL. Our results enrich the understanding of lncRNAs and alternative splicing in regulating the odontoblast differentiation of hDPSCs, and provide clues to improve the clinical therapeutic potential of hDPSCs for dental pulp restoration.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"149"},"PeriodicalIF":7.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721542","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}