Stem Cells Translational Medicine最新文献

{"title":"Anti-viral CD8 central memory veto cells as a new platform for CAR T cell therapy.","authors":"Wei-Hsin Liu, Anat Globerson Levin, Assaf Lask, Galit Horn, Tova Waks, Bar Nathansohn Levi, Irit Milman Krentsis, Einav Shoshan, Xiaohua Su, Maksim Mamonkin, Richard E Champlin, Yair Reisner, Esther Bachar Lustig","doi":"10.1093/stcltm/szaf020","DOIUrl":"10.1093/stcltm/szaf020","url":null,"abstract":"<p><p>Central memory CD8 T cells exhibit marked veto activity enhancing engraftment in several mouse models of T cell-depleted bone marrow (TDBM) allografting. Graft-versus-host disease (GVHD) can be prevented by stimulation of mouse or human memory CD8 T cells against their cognate antigens under cytokine deprivation, in the early phase of culture followed by further expansion with IL21, IL15, and IL7. Thus, human anti-viral CD8 central memory veto T cells generated from CMV and EBV-positive donors are currently evaluated in a clinical trial at MD Anderson Cancer Centre (MDACC). Results in 15 patients indicate a low risk of GVHD. Considering that these cells could offer an attractive platform for CAR cell therapy, we evaluated methodologies for their effective transduction with 2 retroviral vectors. Initially, a vector directed against Her2 was tested and optimal transduction was attained at day 5 of culture. The transduced cells were expanded for an additional 7 days and exhibited marked anti-tumor reactivity ex-vivo while retaining their veto activity. Transduction with a vector directed at CD19 was effectively attained at days 4-5 allowing for substantial harvest of transduced cells at day 12 of culture. These Veto-CD19CAR central memory CD8 T cells exhibited marked anti-tumor reactivity in-vitro and in-vivo without GVHD, measured following transplantation into immune-deficient mice. These results strongly suggest that Veto-CAR T cells offer an attractive platform for CAR T cell therapy without gene editing for addressing the risk of GVHD or graft rejection.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 6","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192230","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":"Initial or continuous coculture with umbilical cord-derived mesenchymal stromal cells facilitates in vitro expansion of human regulatory T-cell subpopulations.","authors":"Qifeng Ou, Sarah Cormican, Rachael Power, Sarah Hontz, Shirley A Hanley, Md Nahidul Islam, Georgina Shaw, Laura M Deedigan, Emma Horan, Stephen J Elliman, Barbara Fazekas, Janusz Krawczyk, Neema Negi, Matthew D Griffin","doi":"10.1093/stcltm/szaf012","DOIUrl":"10.1093/stcltm/szaf012","url":null,"abstract":"<p><p>Clinical trials have demonstrated the safety and potential efficacy of ex vivo expanded regulatory T cells (Tregs) for immune-mediated diseases. Nonetheless, achieving consistent and timely Treg yield and purity remains challenging. We aimed to evaluate the potential to enhance culture expansion of primary human total Treg (CD4+/CD25+/CD127lo) and Treg subpopulations through coculture with human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs). In 14- to 21-day anti-CD3/anti-CD28-, interleukin-2-, and rapamycin-containing cultures, fluorescence-activated cell sorting (FACS)-purified total Treg underwent 4-fold greater expansion following hUC-MSC coculture. Potency to suppress T effector cell (Teff) proliferation was equivalent for hUC-MSC-cocultured and control Tregs and correlated with the expression of HLA-DR, CD39, and inducible costimulator (ICOS). The impact of hUC-MSC coculture on ex vivo expansion of 3 FACS-purified Treg subpopulations [CD45RA+ (Subtype I), CD45RA-HLA-DR+ (Subtype II), and CD45RA-HLA-DR- (Subtype III)] was then investigated. Both initial and continuous hUC-MSC coculture yielded significantly higher fold expansion of each Treg subpopulation compared to control. However, the magnitude of enhancement was substantially greater for non-naive (Subtypes II and III) than for naive (Subtype I) Treg. Coculture with hUC-MSC increased HLA-DR expression of all 3 expanded Treg subpopulations while maintaining comparable Teff suppressive potency. For non-naive Treg (Subtypes II and III), both initial and continuous hUC-MSC coculture also increased the final %Foxp3+ and %Helios+. Thus, coculture with clinical-grade hUC-MSC substantially enhances the ex vivo yield, preserves the suppressive potency, and modulates HLA-DR expression of FACS-purified Treg subpopulations with greatest effect on non-naive (CD45RA-) Treg. The findings have potential to facilitate identification, functional characterization, and manufacturing of Treg subpopulations with distinct therapeutic benefits.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 6","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294945","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: Mesenchymal stromal cells-derived small extracellular vesicles protect against UV-induced photoaging via regulating pregnancy zone protein.","authors":"","doi":"10.1093/stcltm/szaf028","DOIUrl":"10.1093/stcltm/szaf028","url":null,"abstract":"","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 6","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294943","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":"DLK1-expressing neural progenitor cells promote tissue repair and functional recovery after cervical spinal cord injury.","authors":"Nader Hejrati, Zijian Lou, Sogolie Kouhzaei, Oliver Zhang, Jian Wang, Mohamad Khazaei, Michael G Fehlings","doi":"10.1093/stcltm/szaf014","DOIUrl":"10.1093/stcltm/szaf014","url":null,"abstract":"<p><p>Spinal cord injury (SCI) elicits a hostile microenvironment characterized by inflammation, gliosis, and disrupted signaling pathways that collectively impede neural repair. Neural progenitor cells (NPCs) represent a promising regenerative approach, yet their survival and differentiation are often compromised in this setting. Here, we investigated whether engineering NPCs to overexpress the Notch pathway modulator Delta-like non-canonical Notch ligand 1 (DLK1) could overcome these limitations and improve functional outcomes after cervical SCI in rats. NPCs were engineered to express DLK1 under a Pax6 promoter-driven expression system, ensuring elevated DLK1 levels during the progenitor state. Following transplantation of DLK1-overexpressing NPCs or control NPCs, we assessed graft survival, lineage differentiation, behavioral performance, and electrophysiological integration over 12 weeks. DLK1-expressing NPCs exhibited significantly greater retention in the injured spinal cord and showed enhanced neuronal differentiation alongside reduced astrocytic commitment compared to controls. Behavioral tests-including forelimb grip strength and CatWalk gait assessments-demonstrated that DLK1-modified NPCs conferred robust improvements in forelimb motor coordination and overall locomotion. Concordantly, electrophysiological recordings revealed increased motor-evoked potential amplitudes and area-under-the-curve values in animals receiving DLK1-transduced NPC grafts, indicative of strengthened synaptic integration within the host motor circuitry.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 6","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192231","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: Upregulating CXCR4 in Human Fetal Mesenchymal Stem Cells Enhances Engraftment and Bone Mechanics in a Mouse Model of Osteogenesis Imperfecta.","authors":"","doi":"10.1093/stcltm/szaf027","DOIUrl":"10.1093/stcltm/szaf027","url":null,"abstract":"","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 6","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294944","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":"Nutraceuticals: using food to enhance brain health by modulating postnatal neurogenesis in animal models and patient populations.","authors":"Jun Ong, Qingqing Wu, Kazunori Sasaki, Hiroko Isoda, Francis G Szele","doi":"10.1093/stcltm/szaf006","DOIUrl":"10.1093/stcltm/szaf006","url":null,"abstract":"<p><p>Adult hippocampal neurogenesis, while occurring throughout life, decreases with age and in some neurodegenerative diseases. As decreased hippocampal neurogenesis is correlated with cognitive decline, efforts have been made to increase levels of neurogenesis, either through natural compounds, environmental interventions or novel pharmacological compounds. Nutraceuticals are food products with medical benefits such as antioxidation, anti-inflammation or neuroprotection. There has been increasing interest in these \"functional foods\" and their active compounds in recent years, providing natural alternatives to de novo pharmaceuticals. This review highlights key nutraceuticals that promote neurogenesis and/or improve cognitive outcomes. By outlining the effects of these compounds in the animal models employed and in clinical populations, we also suggest further investigations. We examine common targets and pathways through which these nutraceuticals are believed to exert pro-neurogenic effects. Most nutraceutical preparations contain multiple components, any of which may exert effects on neurogenesis. Identifying key active compounds in nutraceuticals may enable researchers to better understand their effects and standardize doses across studies. The less stringent regulatory requirements for nutraceuticals can be a double-edged sword. While allowing easier access to the beneficial effects, higher doses of these compounds may have detrimental effects. Hence, research in this field should not only aim to identify the benefits of these compounds but also to identify efficacious and safe dosages for them. Our aims are to provide understanding of nutraceuticals, provide evidence for their benefits on neurogenesis and neurogenesis-related behaviors and finally to summarize potential mechanisms and help guide future work.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 5","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094846","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":"Emerging clinical applications of ADAR based RNA editing.","authors":"Joseph Rainaldi, Prashant Mali, Sami Nourreddine","doi":"10.1093/stcltm/szaf016","DOIUrl":"10.1093/stcltm/szaf016","url":null,"abstract":"<p><p>RNA editing via adenosine deaminases acting on RNA (ADARs) offers precise and reversible modifications at the RNA level, complementing traditional DNA-targeting therapies. ADAR enzymes catalyze the conversion of adenosine to inosine within double-stranded RNA, influencing critical cellular processes such as translation, splicing, and RNA stability. Utilizing endogenous ADARs guided by exogenous guide RNAs enables site-specific RNA editing without the need for transgenic editor expression, minimizing immunogenicity, and enhancing control over gene expression. Towards addressing the challenges in ensuring specificity, optimizing delivery methods, and navigating regulatory landscapes, ongoing innovations in guide RNA design, delivery technologies, and computational modeling are propelling the field forward. Already, initial clinical advancements are demonstrating the potential of ADAR-mediated RNA editing in treating human diseases. Collaborative efforts among researchers, clinicians, and industry partners are overcoming existing hurdles, progressively positioning ADAR-mediated RNA editing to revolutionize personalized medicine and provide effective treatments for a wide array of historically intractable diseases.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 5","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151821","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: 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/szaf021","DOIUrl":"10.1093/stcltm/szaf021","url":null,"abstract":"","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 5","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151818","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":"Diet, dementia, and the hippocampus.","authors":"Frederick Charles Campbell","doi":"10.1093/stcltm/szaf007","DOIUrl":"10.1093/stcltm/szaf007","url":null,"abstract":"","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 5","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094838","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":"Long term event-free survival following cell-based therapy in patients with cardiomyopathy: the HYPERION observational cohort.","authors":"Russell G Saltzman, Andrew Sundin, Lina V Caceres, Jairo A Tovar, Ana Maria Garzon, Maria A Cabreja, Hossein Shayestehyekta, Jeanette Soto, Dushyantha Jayaweera, Aisha Khan, Ivonne H Schulman, Raul D Mitrani, Joshua M Hare","doi":"10.1093/stcltm/szaf010","DOIUrl":"10.1093/stcltm/szaf010","url":null,"abstract":"<p><strong>Introduction: </strong>There is limited long-term clinical outcome data supporting the use of cell-based therapy to treat heart failure. The HYPERION study (NCT03071835) followed long-term outcomes of patients with ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NIDCM) who received mesenchymal stromal cells (MSC). We hypothesized that improved cardiac parameters predict longer event-free survival.</p><p><strong>Methods: </strong>We performed a Kaplan-Meier analysis to examine event-free survival as the primary outcome. Time-to-event information was captured from all eligible participants. Endpoint events were defined as death (all-cause), Left Ventricular Assist Device (LVAD) placement, or Heart Transplant. Subjects were categorized based on increase in Left Ventricular Ejection Fraction (LVEF) or decrease in Left Ventricular End Diastolic Volume (LVEDV) for comparisons within disease etiologies.</p><p><strong>Results: </strong>There were 134 men and 21 women, with mean age 60.0 ± 11.0 years. There were 121 (78%) with ICM and 34 (22%) with NIDCM. By the end of long-term follow-up (~13 years), 38 (24.5%) subjects had deceased, 5 (3.2%) received LVAD, and 8 (5.2%) underwent heart transplantation. Post-therapy increase of ≥5% LVEF was associated with longer event-free survival in NIDCM (HR:0.31; 95%CI, 0.11,0.86; P = .025), but not ICM (HR:1.14; 95%CI, 0.47,2.72; P = .776). Conversely, reduction in left ventricular end-diastolic volume (LVEDV) was associated with longer event-free survival in ICM (HR:0.16; 95%CI, 0.05, 0.55; P = .008) but not NIDCM (HR:0.35; 95%CI, 0.1,1.2; P = .098). ICM improvers had LVEDV of 225.7 ± 95.9 mL at baseline and 209.0 ± 100.6 mL by year 5 (P = .046). NIDCM improvers had LVEF of 27.2 ± 8.9% at baseline and 36.1 ± 11.6% by year 5 (P = .018).</p><p><strong>Conclusion: </strong>In this long-term observational cohort analysis, improvement of LVEF and/or reduction in LVEDV was associated with survival benefits among subjects with NIDCM and ICM, respectively. In both etiologies the respective improvements are sustained for up to 5 years, providing evidence that cell-based therapy may be a promising and durable treatment option for patients with heart failure.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 5","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151797","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}