Stem Cells Translational Medicine最新文献

{"title":"Expression of Concern: Fate and Efficacy of Engineered Allogeneic Stem Cells Targeting Cell Death and Proliferation Pathways in Primary and Brain Metastatic Lung Cancer.","authors":"","doi":"10.1093/stcltm/szae012","DOIUrl":"10.1093/stcltm/szae012","url":null,"abstract":"","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692972","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":"3' UTR-truncated HMGA2 promotes erythroblasts production from human embryonic stem cells.","authors":"Tiantian Cui, Xiaoling Wang, Ruge Zang, Lingping Zhao, Hao Yan, Xuan Li, Zhenzhao Xu, Haiyang Wang, Junnian Zhou, Yiming Liu, Wen Yue, Xuetao Pei, Jiafei Xi","doi":"10.1093/stcltm/szaf001","DOIUrl":"10.1093/stcltm/szaf001","url":null,"abstract":"<p><p>Cultured red blood cells represent an alternative resource for blood transfusions. However, important issues such as low yields and high costs remain. Recently, gene editing of hematopoietic stem cells has been conducted to induce erythroid differentiation in vitro for producing sufficient RBCs to meet the imbalance in blood supply and demand. The differentiation and expansion of hematopoietic stem and progenitor cells are regulated by transcription factors, such as high mobility group AT-hook 2 (HMGA2). In this study, we utilized CRISPR/Cas9 to establish a doxycycline-inducible HMGA2-expressing human embryonic stem cell (hESC) line. In a defined erythroid differentiation system, HMGA2 prolonged erythroid differentiation in vitro, enabling extensive expansion of human erythroblasts. The erythroblasts derived from the HMGA2-expressing hESC line are rich in polychromatic and orthochromatic erythroblasts expressing mostly α- and γ-globin and have the capacity to differentiate into RBCs. Our findings highlight the potential of combining hematopoietic transcription factors with genome editing techniques to enhance RBC production.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256818","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":"Factor 3 regulates airway engraftment by human bronchial basal cells.","authors":"Susan D Reynolds, Cynthia L Hill, Alfahdah Alsudayri, Jacob T Stack, Kimberly M Shontz, Gianni Carraro, Barry R Stripp, Tendy Chiang","doi":"10.1093/stcltm/szae084","DOIUrl":"10.1093/stcltm/szae084","url":null,"abstract":"<p><p>Cystic fibrosis transmembrane conductance regulator (CFTR) gene editing and transplantation of CFTR-gene corrected airway basal cells has the potential to cure CF lung disease. Although mouse studies established that cell transplantation was feasible, the engraftment rate was typically low and frequently less than the estimated therapeutic threshold. The purpose of this study was to identify genes and culture conditions that regulate the therapeutic potential of human bronchial basal cells. Factor 3 (F3, Tissue Factor 1) is a component of the extrinsic coagulation pathway and activates a cascade of proteases that convert fibrinogen to fibrin. Based on reports that F3 was necessary for human basal cell survival and adhesion in vitro, the present study evaluated F3 as a potential determinant of therapeutic fitness. The gene expression profile of F3 mRNA-positive human bronchial basal cells was evaluated by scRNAseq and the impact of the lung environment on F3 expression was modeled by varying in vitro culture conditions. F3 necessity for adhesion, proliferation, and differentiation was determined by CRISPR/Cas9 knockout (KO) of the F3 gene. Finally, the impact of F3 manipulation on engraftment was determined by orthotropic co-transplantation of wild-type and F3-KO cells into the airways of immunocompromised mice. In contrast with the hypothesis that F3 increases the therapeutic fitness of basal cells, F3 expression decreased engraftment. These studies guide the ongoing development of cellular therapies by showing that in vitro assessments may not predict therapeutic potential and that the lung milieu influences the functional properties of transplanted bronchial basal cells.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562838","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":"Development and intra-renal delivery of renal progenitor organoids for effective integration in vivo.","authors":"Diana Lim, Ickhee Kim, Qianqian Song, Ji Hyun Kim, Anthony Atala, John D Jackson, James J Yoo","doi":"10.1093/stcltm/szae078","DOIUrl":"10.1093/stcltm/szae078","url":null,"abstract":"<p><p>Renal progenitor organoids have been proposed as a source of tissue for kidney regeneration; however, their clinical translatability has not been demonstrated due to an inability to mass-produce comprehensive renal progenitor organoids and the lack of an effective intra-renal delivery platform that facilitates rapid integration into functionally meaningful sites. This study addresses these shortcomings. Human-induced pluripotent stem cells were differentiated into renal progenitor cells using an established protocol and aggregated using a novel assembly method to produce high yields of organoids. Organoids were encapsulated in collagen-based scaffolds for in vitro study and in vivo implantation into mouse renal cortex. In vitro, the organoids demonstrated sustained cell viability and renal structure maturation over time. In vivo delivered organoids showed rapid integration into host renal parenchyma while showing tubular and glomerular-like structure development and maturity markers. This proof-of-concept study presents many promising results, providing a system of renal organoid formation and delivery that may support the development of clinically translatable therapies and the advancement of in vitro renal organoid studies.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523118","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":"Human umbilical cord mesenchymal stem cells small extracellular vesicles-derived miR-370-3p inhibits cervical precancerous lesions by targeting DHCR24.","authors":"Weizhao Li, Chi Zhang, Tianshun Gao, Yazhou Sun, Huan Yang, Lixiang Liu, Ming Shi, Lu Ding, Changlin Zhang, David Y B Deng, Tian Li","doi":"10.1093/stcltm/szae087","DOIUrl":"10.1093/stcltm/szae087","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer is often caused by persistent high-risk human papillomavirus (HPV) infection, causing precancerous lesions. Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEV) exhibit diverse effects on tumors. This study investigates hucMSC-sEV, the impact and mechanisms on HPV-positive cervical precancerous lesion cells to provide new treatment insights.</p><p><strong>Materials and methods: </strong>We previously obtained hucMSC and hucMSC-sEV. In vitro experiments evaluated hucMSC-sEV effects on the proliferation and migration of S12 cells (derived from cervical precancerous lesions). Bioinformatics identified key microRNA components, and their impact on S12 cell proliferation and migration was investigated. The target gene of the microRNA component was predicted and confirmed via bioinformatics and dual-luciferase reporter assays. Lentiviral systems overexpressed target gene in S12 cells to examine the effects on microRNA impacts. SH-42 inhibitor was used to investigate target gene treatment potential. Immunohistochemistry assessed target gene expression in cervical precancerous lesions tissue.</p><p><strong>Results: </strong>hucMSC-sEV significantly inhibited S12 cell proliferation and migration. Bioinformatics identified miR-370-3p as an effective cargo, which also suppressed S12 cell proliferation and migration. miR-370-3p was confirmed targeting DHCR24 (24-Dehydrocholesterol Reductase). DHCR24 overexpression reversed miR-370-3p's inhibitory effects, while SH-42 counteracted DHCR24 overexpression's promoting effects. Clinical specimen analysis supported these findings, demonstrating a positive correlation between DHCR24 protein expression and cervical precancerous lesions' progression.</p><p><strong>Conclusions: </strong>hucMSC-sEV inhibits S12 cell proliferation and migration, mediated by miR-370-3p targeting DHCR24 to regulate cellular cholesterol content. DHCR24 inhibition reduces the cholesterol level and cell functions, suggesting its potential as a therapeutic target in cervical precancerous lesions.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649179","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":"Safety and feasibility of umbilical cord blood transplantation in children with neuronal ceroid lipofuscinosis: a retrospective study.","authors":"Andrea Bauchat, Veronika Polishchuk, Vanessa A Fabrizio, Jennifer E Brondon, Kristin M Page, Timothy A Driscoll, Paul L Martin, Kris M Mahadeo, Joanne Kurtzberg, Vinod K Prasad","doi":"10.1093/stcltm/szae080","DOIUrl":"10.1093/stcltm/szae080","url":null,"abstract":"<p><p>Ceroid lipofuscinosis neuronal (CLN) encompasses rare inherited neurodegenerative disorders that present in childhood with clinical features including epilepsy, psychomotor delay, progressive vision loss, and premature death. Published experience utilizing umbilical cord blood transplant (UCBT) for these disorders is limited. This retrospective analysis includes patients with CLN (2, 3, and 5) who underwent UCBT from 2012 to 2020. All subjects (n = 8) received standard-of-care myeloablative conditioning. Four also enrolled in clinical trial NCT02254863 and received intrathecal DUOC-01 cells posttransplant. Median age at UCBT was 5.9 years. All subjects achieved neutrophil engraftment with >95% donor chimerism at a median of 28.5 days. Sinusoidal obstructive syndrome was not observed. Severe acute graft-versus-host disease occurred in 12.5%. Other complications included autoimmune hemolytic anemia (25%) and viral reactivation/infection (62.5%). No transplant-related mortality was observed. Two CLN2 patients died, 1 from progressive disease and 1 from unknown cause at days +362 and +937, respectively. With median follow-up of 8 years, overall survival at 100 days and 24 months was 100% and 88%, respectively. Three of 4 CLN3 subjects stabilized Hamburg motor and language scores. While UCBT appears safe and feasible in these patients, given the variable expression and natural history, extended follow-up and further studies are needed to elucidate the potential impact of UCBT on clinical outcomes.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547552","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 P2X7 receptor antagonism as a therapeutic target for neuroprotection in an hiPSC motor neuron model.","authors":"Alexandra E Johns, Arens Taga, Andriana Charalampopoulou, Sarah K Gross, Khalil Rust, Brett A McCray, Jeremy M Sullivan, Nicholas J Maragakis","doi":"10.1093/stcltm/szae074","DOIUrl":"10.1093/stcltm/szae074","url":null,"abstract":"<p><p>ATP is present in negligible concentrations in the interstitium of healthy tissues but accumulates to significantly higher concentrations in an inflammatory microenvironment. ATP binds to 2 categories of purine receptors on the surface of cells, the ionotropic P2X receptors and metabotropic P2Y receptors. Included in the family of ionotropic purine receptors is P2X7 (P2X7R), a non-specific cation channel with unique functional and structural properties that suggest it has distinct roles in pathological conditions marked by increased extracellular ATP. The role of P2X7R has previously been explored in microglia and astrocytes within the context of neuroinflammation, however the presence of P2X7R on human motor neurons and its potential role in neurodegenerative diseases has not been the focus of the current literature. We leveraged the use of human iPSC-derived spinal motor neurons (hiPSC-MN) as well as human and rodent tissue to demonstrate the expression of P2X7R on motor neurons. We extend this observation to demonstrate that these receptors are functionally active on hiPSC-MN and that ATP can directly induce death via P2X7R activation in a dose dependent manner. Finally, using a highly specific P2X7R blocker, we demonstrate how modulation of P2X7R activation on motor neurons is neuroprotective and could provide a unique pharmacologic target for ATP-induced MN death that is distinct from the role of ATP as a modulator of neuroinflammation.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1198-1212"},"PeriodicalIF":5.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475185","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":"Correction to: Abstract 11: Multicomponent Cord Blood Bank Program, Beyond Transplantation.","authors":"","doi":"10.1093/stcltm/szae082","DOIUrl":"10.1093/stcltm/szae082","url":null,"abstract":"","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1229"},"PeriodicalIF":5.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508288","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":"Second generation multiple channeling using platelet-rich plasma enhances cartilage repair through recruitment of endogenous MSCs in bone marrow.","authors":"Min Ji Lee, Jian Jiang, Soo Hyun Kim, Chris Hyunchul Jo","doi":"10.1093/stcltm/szae075","DOIUrl":"10.1093/stcltm/szae075","url":null,"abstract":"<p><p>In the treatment of cartilage defects, a key factor is the adequate and specific recruitment of endogenous stem cells to the site of injury. However, the limited quantity and capability of endogenous bone marrow stem cells (BM MSCs) often result in the formation of fibrocartilage when using bone marrow stimulation (BMS) procedures. We engineered second-generation platelet-rich plasma (2G PRP) with defibrinogenating and antifibrinolytic agents for injection into the condyle of the right femur, followed by multiple channeling (MCh) 5 days later. This approach aims to enhance repair by promoting the local proliferation and migration of BM MSCs to the full-thickness knee cartilage defect (ftKD). In our in vitro study, 2G PRP increased the number of endogenous BM MSCs and their ability to migrate toward an IL-1β-induced inflammatory condition. This significance was further confirmed by in vivo proliferation results after injection of 2G PRP into the condyle of rats. Fifty-four healthy male Sprague-Dawley rats were divided into 3 groups (ftKD, MCh, 2G MCh) for 3 time points (2 weeks, 4 weeks, 8 weeks). The 2G MCh (2G PRP injection + MCh) groups significantly improved cartilage formation at 4 and 8 weeks compared to the ftKD and MCh groups. The 2G MCh initiated cartilage repair earlier than MCh and significantly enhanced up to 8 weeks. This study demonstrated that 2G PRP increased the number of BM MSCs through the enhancement of proliferation and recruitment into the injured site, thereby improving articular cartilage repair.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1213-1227"},"PeriodicalIF":5.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565055","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":"Correction to: Amnion membrane hydrogel and amnion membrane powder accelerate wound healing in a full thickness porcine skin wound model.","authors":"","doi":"10.1093/stcltm/szae046","DOIUrl":"10.1093/stcltm/szae046","url":null,"abstract":"","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1230"},"PeriodicalIF":5.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913973","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}