STEM CELLS最新文献_第2页

Consistent self-organized emergence of hyaline cartilage in human induced pluripotent stem cell-derived multi-tissue organoids. 在hipsc衍生的多组织类器官中一致的自组织出现透明软骨。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-09-17 DOI: 10.1093/stmcls/sxaf043

Huzefa I Husain, Manci Li, Juan E Abrahante, Natalia Calixto Mancipe, Amanda Vegoe, Yi Wen Chai, Beth Lindborg, Marc Tompkins, Brenda Ogle, Peter A Larsen, Timothy D O'Brien, Ferenc Tóth

{"title":"Consistent self-organized emergence of hyaline cartilage in human induced pluripotent stem cell-derived multi-tissue organoids.","authors":"Huzefa I Husain, Manci Li, Juan E Abrahante, Natalia Calixto Mancipe, Amanda Vegoe, Yi Wen Chai, Beth Lindborg, Marc Tompkins, Brenda Ogle, Peter A Larsen, Timothy D O'Brien, Ferenc Tóth","doi":"10.1093/stmcls/sxaf043","DOIUrl":"10.1093/stmcls/sxaf043","url":null,"abstract":"Existing protocols for in vitro hyaline cartilage production utilizing human induced pluripotent stem cells (hiPSCs) have several challenges including a complex culturing process that uses undefined culture media, phenotypic instability, and batch-to-batch variability of the cell product. Here, our primary objective is to describe a simple, xeno- and feeder-free protocol for the generation of hyaline cartilage utilizing multi-tissue organoids (MTOs). We investigated gene regulatory networks during hiPSC-MTO differentiation using RNA sequencing and bioinformatics analyses, as well as histological and immunohistochemical methods. Interplays between bone morphogenetic protein (BMP) and neural fibroblast growth factor (FGF) pathways associated with the phenotypic transition of MTOs are described. Comparisons across transcriptomes revealed that the expression of chondrocyte-specific genes in MTOs correlates strongly with fetal lower limb chondrocytes. Single-cell RNA sequencing findings confirmed that the majority of cells belonged to the chondrogenic lineage and that they were similar across MTO batches, suggesting uniformity of the culture process. Collectively, these findings demonstrate the consistent emergence of hyaline cartilage in MTOs and the molecular pathways that govern this process, thereby establishing an accessible source of functional chondrocytes for future therapeutic evaluations.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential effects of various cytokine priming on T-cell suppression and migration in canine mesenchymal stem cells. 不同细胞因子启动对犬间充质干细胞T细胞抑制和迁移的差异影响。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-09-17 DOI: 10.1093/stmcls/sxaf044

Chan-Hee Jo, Sang-Yun Lee, Young-Bum Son, Won-Jae Lee, Hyeon-Jeong Lee, Seong-Ju Oh, Chae-Yeon Hong, Yong-Ho Choe, Sung-Lim Lee

{"title":"Differential effects of various cytokine priming on T-cell suppression and migration in canine mesenchymal stem cells.","authors":"Chan-Hee Jo, Sang-Yun Lee, Young-Bum Son, Won-Jae Lee, Hyeon-Jeong Lee, Seong-Ju Oh, Chae-Yeon Hong, Yong-Ho Choe, Sung-Lim Lee","doi":"10.1093/stmcls/sxaf044","DOIUrl":"10.1093/stmcls/sxaf044","url":null,"abstract":"Mesenchymal stem cells (MSCs) have been widely studied for treating immune-mediated diseases due to their immunomodulatory abilities. Recent studies have shown that priming MSCs with inflammatory cytokines can enhance these functions, yet the optimal priming conditions for canine MSCs remain poorly defined. In this study, we investigated the effects of priming canine adipose tissue-derived MSCs (cAMSCs) with inflammatory cytokines IFN-γ, TNF-α, and IL-17 at various concentrations (10, 20, and 50 ng/mL) to evaluate their immunomodulatory and migratory capacities. Of the 3 cytokines evaluated, only IFN-γ priming significantly enhanced the expression of immunosuppressive genes IDO and PD-L1, and robustly suppressed T-cell proliferation across all concentrations compared to naïve cAMSCs in both direct co-culture and indirect (conditioned medium) assays. TNF-α priming significantly increased HGF expression and promoted cell cycle progression, while IL-17 priming upregulated COX2 and TGF-β expression; however, both exhibited limited immunomodulatory effects compared to IFN-γ. In addition, IFN-γ induced strong expression of adhesion and migration-related genes, including E-CADHERIN, ICAM1, and VCAM1, and promoted cAMSCs migration in a wound healing assay. Despite increasing MHC II, IFN-γ did not induce CD80, preserving the low immunogenic profile of cAMSCs. These findings support IFN-γ priming as the most effective strategy to enhance the immunomodulatory and migratory functions of cAMSCs, offering substantial potential for MSC-based therapies in veterinary medicine.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-cell analysis of heterogeneity and molecular changes in cultured corneal epithelial stem cells during serial passage. 培养角膜上皮干细胞序列传代过程中异质性和分子变化的单细胞分析。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-09-17 DOI: 10.1093/stmcls/sxaf041

Usanee Reinprayoon, Supaporn Khramchantuk, Natthida Kittimawikrom, Praewphan Ingrungruanglert, Sarinya Phodang, Thanakorn Jaemthaworn, Sira Sriswasdi, Nipan Israsena

{"title":"Single-cell analysis of heterogeneity and molecular changes in cultured corneal epithelial stem cells during serial passage.","authors":"Usanee Reinprayoon, Supaporn Khramchantuk, Natthida Kittimawikrom, Praewphan Ingrungruanglert, Sarinya Phodang, Thanakorn Jaemthaworn, Sira Sriswasdi, Nipan Israsena","doi":"10.1093/stmcls/sxaf041","DOIUrl":"10.1093/stmcls/sxaf041","url":null,"abstract":"The maintenance of corneal epithelial homeostasis relies on limbal stem cells (LSCs) located at the limbus. Although short-term cultured LSC transplantation effectively treats LSC deficiency, prolonged culture leads to stemness loss and abortive colony formation, and the mechanisms remain elusive. In this study, we employed single-cell transcriptomics to investigate LSC population dynamics and changes in gene expression during extended serial culture. Transcriptomic data from 22 708 cells revealed 19 clusters, identifying 3 distinct limbal progenitor populations (Progenitors 1-3) with unique transcriptional profiles and cell division kinetics. All progenitor subgroups expressed stemness-related genes such as ANLN, AURKB, and HMGB2 and were detected at all stages of the cell cycle. Notably, Progenitor3 exhibited the highest levels of genes associated with stemness and the G2/M checkpoint, including ANLN, PLK1, AURKA, HMGB2, and TOP2A, and had the largest proportion of cells in G2/M. Progenitor2 was marked by histone H1 expression, while Progenitor1 displayed distinctive cell cycle kinetics. Despite stable proportions of the three progenitor populations throughout prolonged passaging, mitochondrial gene downregulation, and ribosomal gene upregulation were observed. Treatment with the small molecule RepSox partially preserved LSC maintenance in long-term culture by inhibiting the epithelial-mesenchymal transition program and modulating energy and metabolic pathways. These findings provide insights for optimizing in vitro LSC expansion for cell-based therapies.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Erythropoietin-dependent Acquisition of CD71hiCD105hi Phenotype within CD235a- Early Erythroid Progenitors. CD235a-早期红系祖细胞中CD71hiCD105hi表型的促红细胞生成素依赖性获得

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-09-16 DOI: 10.1093/stmcls/sxaf061

Natascha Schippel, Mrinalini Kala, Shalini Sharma

{"title":"Erythropoietin-dependent Acquisition of CD71hiCD105hi Phenotype within CD235a- Early Erythroid Progenitors.","authors":"Natascha Schippel, Mrinalini Kala, Shalini Sharma","doi":"10.1093/stmcls/sxaf061","DOIUrl":"10.1093/stmcls/sxaf061","url":null,"abstract":"The development of committed erythroid progenitors and their continued maturation into erythrocytes requires the cytokine erythropoietin (Epo). Here, we describe the immunophenotypic identification of a CD34- colony-forming unit-erythroid (CFU-E) progenitor subtype, termed late CFU-E (lateC), that arises in an Epo-dependent manner during human early erythropoiesis (EE). LateC cells lack CD235a (glycophorin A) but have high levels of CD71 and CD105, characterized as Lin-CD123-CD235a-CD49d+CD117+CD34-CD71hiCD105hi. Analysis of ex vivo cultures of bone marrow (BM) CD34+ cells showed that acquisition of the CD71hiCD105hi phenotype in lateC occurs through the formation of four other EE subtypes. Of these, two are CD34+ burst-forming unit-erythroid (BFU-E) cells, distinguishable as CD71loCD105lo early BFU-E (earlyB) and CD71hiCD105lo late BFU-E (lateB), and two are CD34- CFU-E, also distinguishable as CD71loCD105lo early CFU-E (earlyC) and CD71hiCD105lo mid CFU-E (midC). The EE transitions are accompanied by a rise in CD36 expression, such that all lateC cells are immunophenotypically CD36+. Patterns of CD34, CD36, and CD71 indicate two differentiation routes-in one earlyB lose CD34 to form earlyC, and in another, earlyB gain CD36 and CD71hi expression prior to losing CD34 to form midC, bypassing the earlyC stage. Regardless of the route, the transition from midC to lateC requires Epo. All five EE subtypes could be prospectively detected in human BM cells and, upon isolation and reculture, exhibited the potential to continue differentiating along the erythroid trajectory. Finally, we find that all five EE populations can also be detected in cultures of cord blood-derived CD34+ cells at levels similar to those observed in BM CD34+ cell cultures.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PNO1 served as a potential biomarker to promote the stemness and progression of breast cancer via the NF-κB signaling pathway. PNO1可能通过NF-κB信号通路促进乳腺癌的发生和发展。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-09-14 DOI: 10.1093/stmcls/sxaf060

Xiaorui Wang, Ping Yue, Dongming Liu, Xinrui Wen, Xiehua Zhang, Bo Sun, Yi Luo, Liwei Chen, Weidong Li, Hong Liu, Yuchao He, Zhongsheng Tong, Hua Guo

{"title":"PNO1 served as a potential biomarker to promote the stemness and progression of breast cancer via the NF-κB signaling pathway.","authors":"Xiaorui Wang, Ping Yue, Dongming Liu, Xinrui Wen, Xiehua Zhang, Bo Sun, Yi Luo, Liwei Chen, Weidong Li, Hong Liu, Yuchao He, Zhongsheng Tong, Hua Guo","doi":"10.1093/stmcls/sxaf060","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf060","url":null,"abstract":"Background: Breast cancer is a highly heterogeneous disease with diverse phenotypes. At present, increasing evidence supports the role of ribosomal biogenesis in human diseases and tumorigenesis. PNO1, as a ribosome assembly factor, plays a key role in the biological synthesis of ribosomes and ribosomal protein mutations associated with human diseases and tumor development. This study explored PNO1's role as a prognostic biomarker for breast cancer.Methods: Clinical samples and online datasets were used to determine PNO1 expression in breast cancers with different molecular phenotypes and clinicopathological subtypes. CCK-8 assays, colony formation assays, wound healing and transwell assays were performed to investigate tumor cell proliferation, migration and invasion. Western blot, flow cytometry, and sphere- formation assays were used to assess the effect of PNO1 on breast cancer stemness. RNA-sequencing analysis was also performed to elucidate the underlying mechanism.Results: Result showed that the expression level of PNO1 was upregulated in breast cancer samples. In addition, high PNO1 expression was positively correlated with poor survival in breast cancer patients with different molecular types. Moreover, PNO1 was associated with breast cancer heterogeneity by promoting its stem-like properties both in vitro and in vivo through the NF-κB signaling pathway which can be suppressed by JSH-23.Conclusions: Our study found that PNO1 expression was positively correlated with poor survival in different molecular subtypes of breast cancer, and that PNO1 promoted stem-like properties of breast cancer by activating NF-κB activity. Collectively, PNO1 is a potential prognostic biomarker that plays an important role in breast cancer progression.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The impact of donor and recipient age on post-transplantation clonality in murine haematopoiesis. 供体和受体年龄对小鼠造血移植后克隆性的影响。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-09-04 DOI: 10.1093/stmcls/sxaf059

Lars Thielecke, Kalpana Nattamai, Aishlin Hassan, Ingmar Glauche, Hartmut Geiger, Kerstin Cornils

{"title":"The impact of donor and recipient age on post-transplantation clonality in murine haematopoiesis.","authors":"Lars Thielecke, Kalpana Nattamai, Aishlin Hassan, Ingmar Glauche, Hartmut Geiger, Kerstin Cornils","doi":"10.1093/stmcls/sxaf059","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf059","url":null,"abstract":"The sustained production of blood and immune cells is driven by a pool of hematopoietic stem cells (HSCs) and their offspring. Due to the intrinsic heterogeneity of HSCs, the composition of emergent clones changes over time, leading to a reduced clonality in aging mice and humans. Theoretical analyses suggest that clonal conversion rates and clonal complexity depend not only on HSC heterogeneity, but also on additional stress conditions. These insights are particularly relevant in the context of stem cell transplantations, which still remain the only curative option for many hematologic diseases, increasingly considered viable for elderly individuals. However, age-related clonal changes post-transplantation are not well understood. To address this, we conducted a barcode-based assessment of clonality to investigate post-transplantation changes in both homo- and hetero-chronic settings, combined with low- and high-intensity pre-conditioned recipients. A robust and polyclonal engraftment was observed across all groups, but with distinct differences in barcode diversity. In particular, transplanted aged HSCs showed no changes in clonality, regardless of recipient age or pre-conditioning. Young HSCs transplanted into severely pre-conditioned old hosts as well as under reduced pre-conditioning, allowed for full lymphoid reconstitution, but showed substantial differences in clonality. Also, myeloid lineage bias, a hallmark of aged HSCs, was confirmed at a clonal level across all experimental groups. Overall, we found that aged HSCs generally maintain clonal diversity similar to young HSCs, but notable differences emerge under hetero-chronic conditions and varying pre-conditioning regimens. These findings challenge current paradigms and underscore the complex interactions between aging and transplantation conditions.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular signature and regulatory network of human umbilical cord mesenchymal stromal cells as a niche for hematopoietic stem cells and progenitors. 人脐带间充质间质细胞作为造血干细胞和祖细胞生态位的分子特征和调控网络。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-09-02 DOI: 10.1093/stmcls/sxaf057

Pornprapa Srimorkun, Kittisak Suanpan, Korakot Atjanasuppat, Piamsiri Sawaisorn, Werapath Somchit, Teerapong Siriboonpiputtana, Oytip Nathalang, Suradej Hongeng, Sawang Petvises, Usanarat Anurathapan

{"title":"Molecular signature and regulatory network of human umbilical cord mesenchymal stromal cells as a niche for hematopoietic stem cells and progenitors.","authors":"Pornprapa Srimorkun, Kittisak Suanpan, Korakot Atjanasuppat, Piamsiri Sawaisorn, Werapath Somchit, Teerapong Siriboonpiputtana, Oytip Nathalang, Suradej Hongeng, Sawang Petvises, Usanarat Anurathapan","doi":"10.1093/stmcls/sxaf057","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf057","url":null,"abstract":"The fate of hematopoietic stem cells (HSCs) is determined by a complex regulatory network supporting self-renewal and quiescence within a niche. Umbilical cord mesenchymal stromal cells (UC-MSCs) are classified as an alternative niche for the expansion of hematopoietic stem and progenitor cells (HSPCs). The molecular mechanisms by which UC-MSCs regulate hematopoiesis are still not fully understood. In this study, the cocultures of UC-MSCs and umbilical cord blood CD34+ (UCB-CD34+) cells were established. Immunophenotype, cell proliferation, and hematopoietic function of UCB-CD34+ cells were evaluated on days 0 to 7. UC-MSCs promoted UCB-CD34+ cell proliferation but were less effective at preserving their stemness. Notably, UC-MSCs promoted the myeloid lineage commitment, significantly observed on day 3. Integrative transcriptomic analysis highlighted the molecular signature and regulatory networks of UC-MSCs. The long non-coding RNA (lncRNA)-RNA binding protein (RBP) interaction network and lncRNA cis- and trans-regulatory networks were evident. The significant 3-gene modules and a set of 10-hub genes were identified in the protein-protein interaction (PPI) network, including RPS16, CD74, RPL35, COX7C, RPL38, RPS28, RPS27, RPS10, TARDBP, and TOMM7. These findings exemplify the niche activity of UC-MSCs in regulating cell differentiation, genomic stability maintenance, and modulation of the hematopoietic supportive niche. The transcriptional landscape, together with the identified regulatory networks, gene modules, and key hub genes provide new insights into the molecular mechanisms of UC-MSCs and establish a basis for refining ex vivo culture systems for therapeutic HSC expansion.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Giant Panda Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Promote Dermal Fibroblast Proliferation and Wound Healing. 大熊猫脐带间充质干细胞衍生外泌体促进真皮成纤维细胞增殖和伤口愈合。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-08-22 DOI: 10.1093/stmcls/sxaf051

Yuliang Liu, Hongyan Li, Yuan Li, Donghui Wang, Jiasong Chen, Zhixiang Yuan, Rongrui Zhang, Mingyue Zhang, Zhigang Cai, Rong Hou, Junhui An

{"title":"Giant Panda Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Promote Dermal Fibroblast Proliferation and Wound Healing.","authors":"Yuliang Liu, Hongyan Li, Yuan Li, Donghui Wang, Jiasong Chen, Zhixiang Yuan, Rongrui Zhang, Mingyue Zhang, Zhigang Cai, Rong Hou, Junhui An","doi":"10.1093/stmcls/sxaf051","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf051","url":null,"abstract":"Umbilical cord mesenchymal stem cell-derived exosomes (UC-MSC-Exos) represent a potential therapeutic solution for captive giant pandas. The aim of this study was elucidating the proteomic and microRNA (miRNA) profiles and discerning their functional roles constitutes an essential step towards comprehending their therapeutic mechanisms and optimizing their application in giant pandas. UC-MSC-Exos, isolated from the culture supernatant of giant panda umbilical cord mesenchymal stem cells (UC-MSCs) using classic ultracentrifugation, were characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting (WB). Mass spectrometry analysis and high-throughput small RNA sequencing were performed to determine the proteomic and miRNA profiles. Further elucidation of the mechanism underlying the impact of miR-21-5p on DFs proliferation was achieved through dual-luciferase gene reporter assays. UC-MSC-Exos enhanced the proliferation and migration of giant panda dermal fibroblasts (DFs). These effects are partially attributed to growth factors such as platelet-derived growth factor (PDGF), transforming growth factor-β1 (TGF-β1), basic-fibroblast growth factor (b-FGF), and miR-21-5p. We found that miR-21-5p contributes to fibroblast proliferation by targeting the programmed cell death 4 (PDCD4) and reversion inducing cysteine rich protein with kazal motifs (RECK) genes, attenuating the expression of α-smooth muscle actin (α-SMA) induced by TGF-β1, and impeding the differentiation of fibroblasts into myoblasts. This study serves as a foundational framework for elucidating the functional properties of giant panda UC-MSC exosomes and offers valuable technical insights for the development of novel strategies to enhance wound healing in giant pandas.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel trained mesenchymal stromal cell-based therapy, HXB-319, effectively controls progressive glomerulonephritis in a murine lupus model. HXB-319是一种基于间充质细胞的新型疗法，可有效控制小鼠狼疮模型的进行性肾小球肾炎。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-08-22 DOI: 10.1093/stmcls/sxaf040

Hulya Bukulmez, Adrienne T Dennis, Jane Reese-Koc, Sarah Kleinsorge-Block, Scott Sieg, Kristin B Highland, Steven N Emancipator

{"title":"A novel trained mesenchymal stromal cell-based therapy, HXB-319, effectively controls progressive glomerulonephritis in a murine lupus model.","authors":"Hulya Bukulmez, Adrienne T Dennis, Jane Reese-Koc, Sarah Kleinsorge-Block, Scott Sieg, Kristin B Highland, Steven N Emancipator","doi":"10.1093/stmcls/sxaf040","DOIUrl":"10.1093/stmcls/sxaf040","url":null,"abstract":"Introduction: Systemic lupus erythematosus (SLE) is driven by abnormal type-I and -II interferon activation, affecting a variety of immunocompetent cells. Mesenchymal stromal cells (MSCs) can modulate inflammation but often lack consistent potency. We developed HXB-319, an MSC-based therapy targeting inflammatory pathways in SLE. Previously, HXB-319 was shown to reduce alveolar hemorrhage in an SLE model. Here, we report its effects in a model of SLE that progresses to end stage kidney disease.Materials and methods: SLE-like disease was induced via intraperitoneal (IP) pristane injection in female BALB/cJ mice, followed by treatment with naïve MSCs or HXB-319. Over 9 months, survival and proteinuria were monitored. Upon euthanasia, kidneys were analyzed for histopathology and gene expression, splenocytes for immune subsets by flow cytometry, and serum for autoantibodies, growth factors, and cytokines.Results: HXB-319 significantly altered plasmacytoid dendritic cells, CD4+PD-L1+ cells, and both CD4+ and CD8+ RORγt+ (Th17 cells) subsets. HXB-310 lowered IFN-γ (P < 0.001), IL-17A (P = 0.01), BAFF (P < 0.05), and anti-dsDNA (P < 0.05), compared to untreated mice. HXB-319, but not naïve MSCs, significantly improved survival, halted progression of kidney disease, and stabilized proteinuria (all P < 0.05).Conclusion: HXB-319 demonstrates potential for mitigating SLE-associated glomerulonephritis, improving survival, and reducing proteinuria and glomerulosclerosis.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stem cells within the HPA axis in tissue homeostasis and disease. HPA轴内的干细胞在组织稳态和疾病中的作用。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-08-22 DOI: 10.1093/stmcls/sxaf039

Mario Schubert, Kaomei Guan, Charlotte Steenblock

{"title":"Stem cells within the HPA axis in tissue homeostasis and disease.","authors":"Mario Schubert, Kaomei Guan, Charlotte Steenblock","doi":"10.1093/stmcls/sxaf039","DOIUrl":"10.1093/stmcls/sxaf039","url":null,"abstract":"The hypothalamus-pituitary-adrenal (HPA) axis is crucial for energy metabolism, cardiovascular function, and stress response. Importantly, neuronal signaling circuits in the hypothalamus, along with hormones released from the pituitary and adrenal gland, must adapt to physiological demands or pathological conditions. Stem and progenitor cells are pivotal in this regulation, either by giving rise to distinct cell types or by interacting with progenitor or hormone-producing cells. While lineage-tracing studies in rodent models have explored the role of stem cells in the HPA axis, our understanding of the mechanisms underlying this dynamic tissue plasticity remains limited, especially in humans. Moreover, single-cell RNA sequencing has revealed significant heterogeneity among stem cell populations in the HPA-axis, raising questions about the functional relevance of individual subclusters during development and adulthood. In this concise review, we summarize current knowledge on stem cells in the HPA axis, focusing on their origins, localization of different stem cell populations, and sex-specific activity in maintaining tissue integrity. We further address their role under pathophysiological conditions, including metabolic disease, cancer, and stress. Lastly, we discuss emerging strategies for replacing lost or damaged stem or progenitor cells during aging, highlighting recent achievements in the in vitro differentiation of hypothalamic, pituitary, and adrenal stem cells.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0