Stem Cells Translational Medicine最新文献

{"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":4.9,"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}

{"title":"A single-center, phase 1/2a trial of hESC-derived mesenchymal stem cells (MR-MC-01) for safety and efficacy in interstitial cystitis patients.","authors":"Yoon Soo Kyung, Ki-Sung Hong, Hyung-Min Chung, Jung Hyun Shin, Myung-Soo Choo, Eun-Young Kim, Jeong Min Shin, Ah Reum Kang, Jin Won Seo, Juhyun Park, Se-Pill Park","doi":"10.1093/stcltm/szaf018","DOIUrl":"10.1093/stcltm/szaf018","url":null,"abstract":"<p><p>This study investigated the safety and efficacy of MR-MC-01, a mesenchymal stem cell therapy derived from human embryonic stem cells, in patients with interstitial cystitis (IC), particularly those with Hunner lesions unresponsive to pentosan polysulfate sodium (PPS). Conducted as a prospective, randomized, double-blind, placebo-controlled phase I/IIa clinical trial, it enrolled 22 patients, with six completing phase I and 16 participating in phase IIa. Phase I tested 2 doses (2.0 × 107 and 5.0 × 107 cells) to determine the maximum tolerated dose (MTD), revealing no dose-limiting toxicities and only mild adverse events such as transient hemorrhage and bladder pain. In phase IIa, 12 participants received the MTD of 5.0 × 107 cells, and 4 received placebo. Significant reductions in interstitial cystitis questionnaire (ICQ) and pain urgency frequency (PUF) scores were observed in the treatment group. Improvements were noted in nocturnal voiding frequency and Hunner lesion size, with 8 patients showing either a reduction or complete resolution of lesions after 6 months. The global response assessment (GRA) reported moderate to marked improvement in 41.67% of treated patients versus 25% in the placebo group. MR-MC-01 demonstrated no serious drug-related adverse events, highlighting its favorable safety profile. These findings suggest that MR-MC-01 not only alleviates symptoms but also promotes structural recovery in IC, making it a promising treatment option. Further large-scale, long-term studies are warranted to confirm these results and optimize therapeutic protocols. (Identifier: NCT04610359).</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/PMC12087345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094762","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":"Zinc finger protein 750 is a novel regulator of osteoblast differentiation and bone homeostasis by transcriptionally deactivating SNAI1 signaling.","authors":"Xiaoli Shi, Xueli Jia, Wei Liu, Liwen Shi, Zheng Yang, Jie Zhou, Xiaoxia Li, Baoli Wang","doi":"10.1093/stcltm/szaf013","DOIUrl":"https://doi.org/10.1093/stcltm/szaf013","url":null,"abstract":"<p><p>Zinc finger protein 750 (ZNF750) has been identified as a potential tumor suppressor across multiple malignancies. Nevertheless, the specific involvement of ZNF750 in the regulation of mesenchymal cell differentiation and bone homeostasis has yet to be elucidated. In the current study, we observed a substantial presence of ZNF750 in bone tissue and noted alterations in its expression during osteogenic differentiation of mesenchymal progenitor cells. Functional experiments indicated that ZNF750 promoted osteogenic differentiation while impeding adipogenic differentiation from mesenchymal stem/progenitor cells. Further mechanistic investigations revealed that ZNF750 transcriptionally suppressed the expression of Snail family transcriptional repressor 1 (SNAI1) by binding to the proximal promoter region of Snai1 gene, thereby activating Wnt/β-catenin signaling. SNAI1 exerted opposing effects on cell differentiation towards osteoblasts and adipocytes in comparison to ZNF750. The overexpression of SNAI1 counteracted the dysregulated osteogenic and adipogenic differentiation induced by ZNF750. Furthermore, the transplantation of Znf750-silenced bone marrow stromal cells into the marrow of wild-type mice resulted in a reduction in cancellous and cortical bone mass, alongside a decrease in osteoblasts and an increase in marrow adipocytes, while the number of osteoclasts remained unchanged. This study presents the first demonstration that ZNF750 regulates the differentiation of osteoblasts and adipocytes from mesenchymal stem/progenitor cells by transcriptionally deactivating SNAI1 signaling, thereby contributing to the maintenance of bone homeostasis. It suggests that ZNF750 may represent a promising therapeutic target for metabolic bone disorders such as osteoporosis.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 4","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose-mesenchymal stem cells enhance the formation of auricular cartilage in vitro and in vivo.","authors":"Dominika Zielinska, Katarzyna Micka-Michalak, Hyrije Ademi, Philip Fisch, Roland Boeni, Thomas Linder, Ueli Moehrlen, Thomas Biedermann, Agnes S Klar","doi":"10.1093/stcltm/szae098","DOIUrl":"https://doi.org/10.1093/stcltm/szae098","url":null,"abstract":"<p><p>Patients suffering from microtia have limited treatment options for auricular reconstruction due to donor-site morbidity, complications, and unaesthetic outcome. Therefore, tissue engineering emerged as an alternative therapeutic option. Here, we generated and characterized human auricular cartilage using differentiated human adipose mesenchymal stem cells (hASCs) combined with human auricular chondrocytes. The differentiated hASCs were analysed for their morphology, phenotype, gene, and protein expression of chondrogenic markers, and biochemical composition at different time points in 2D and 3D in vitro. Importantly, we improved conditions for chondrogenic differentiation of hASCs in vitro to enhance their proliferation, survival, and deposition of cartilaginous-matrix proteins. In particular, gene expression analysis revealed an upregulation of cartilage oligomeric matrix protein (COMP) and aggrecan core protein (ACAN) in hASCs using the improved differentiation protocol in vitro. Additionally, we observed that co-seeding of hASCs with chondrocytes in a 1:5 ratio significantly enhanced the de novo auricular cartilage formation in a collagen-I bioink after 8 weeks on immunodeficient rat. In particular, the co-culture resulted in reduced shrinkage, and increased cartilage matrix production as confirmed by GAG deposition in vivo. Our results demonstrate that in co-cultures, hASCs stimulate cartilage formation due to a synergistic effect: hASCs' differentiation into chondrocytes and a trophic effect of hASCs on human auricular chondrocytes. Here we demonstrate the successful use of an hASC-chondrocyte co-culture technique for auricular cartilage tissue engineering in 3D collagen-I bioink. This co-culture approach omits the major drawbacks of traditional cartilage transplantation and thus, represents a fundamental step towards clinical translation.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 4","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031826","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}