STEM CELLS最新文献

{"title":"Impact of Pro-Inflammatory Cytokine Preconditioning on Metabolism and Extracellular Vesicles in Feline Mesenchymal Stromal Cells: A Preliminary Study.","authors":"Maria Soltero-Rivera, Boaz Arzi, Lynda Bourebaba, Krzysztof Marycz","doi":"10.1093/stmcls/sxaf014","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf014","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have shown promise in treating inflammation. This study investigates whether preconditioning feline adipose-derived stem cells (FeASCs) with inflammatory cytokines, specifically IFN-γ and TNF-α, enhances the anti-inflammatory efficacy of MSC-derived EVs.</p><p><strong>Objective: </strong>We hypothesize that cytokine-primed FeASCs will produce EVs with improved anti-inflammatory properties and that this preconditioning will affect mitochondrial dynamics to enhance EV therapy effectiveness.</p><p><strong>Methods: </strong>FeASCs were exposed to TNF-α / IFN-γ combination to mimic a pro-inflammatory milieu favoring ASCs immunosuppressive phenotype. We analyzed morphological, metabolic, and immunomodulatory characteristics of native and cytokine-primed FeASCs. EVs were assessed for anti-inflammatory and mitochondrial-related markers. We also evaluated mitochondrial function and apoptosis markers in cytokine-primed cells.</p><p><strong>Results: </strong>Cytokine priming led to significant morphological changes in FeASCs, including enhanced cell projections and increased apoptosis. EVs from cytokine-primed FeASCs exhibited a heightened immunomodulatory profile, with increased expression of both pro-inflammatory and anti-inflammatory mediators. Transcriptomic analysis of these EVs revealed the upregulation of genes associated with cell proliferation, survival, and apoptosis. Mitochondrial function was impaired in cytokine-primed cells, but mitochondrial morphology remained unchanged. EVs from these cells contained higher levels of mitochondrial-related transcripts, indicating a compensatory response.</p><p><strong>Conclusion: </strong>Cytokine-primed FeASCs generate EVs with enhanced immunomodulatory potential, highlighting their therapeutic promise. However, further research is needed to validate their efficacy and safety and refine preconditioning strategies to optimize EV-based therapies for inflammatory conditions. These advancements could pave the way for broader applications in regenerative medicine.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762629","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}

{"title":"NK-cell cytotoxicity toward pluripotent stem cells and their neural progeny: impacts of activating and inhibitory receptors and KIR/HLA mismatch.","authors":"Camilla Henden, Hege B Fjerdingstad, Elisabeth G Bjørnsen, Lavanya Thiruchelvam-Kyle, Michael R Daws, Marit Inngjerdingen, Joel C Glover, Erik Dissen","doi":"10.1093/stmcls/sxae083","DOIUrl":"10.1093/stmcls/sxae083","url":null,"abstract":"<p><p>Pluripotent stem cells provide opportunities for treating injuries and previously incurable diseases. A major concern is the immunogenicity of stem cells and their progeny. Here, we have dissected the molecular mechanisms that allow natural killer (NK) cells to respond to human pluripotent stem cells, investigating a wide selection of activating and inhibitory NK-cell receptors and their ligands. Reporter cells expressing the activating receptor NKG2D responded strongly to embryonic stem (ES) cell lines and induced pluripotent stem (iPS) cell lines, whereas reporter cells expressing the activating receptors NKp30, NKp46, KIR2DS1, KIR2DS2, and KIR2DS4 did not respond. Human ES and iPS cells invariably expressed several ligands for NKG2D. Expression of HLA-C and HLA-E was lacking or low, insufficient to trigger reporter cells expressing the inhibitory receptors KIR2DL1, -2DL2, or -2DL3. Similar results were obtained for the pluripotent embryonic carcinoma cell lines NTERA-2 and 2102Ep, and also iPS-cell-derived neural progenitor cells. Importantly, neural progenitor cells and iPS-cell-derived motoneurons also expressed B7H6, the ligand for the activating receptor NKp30. In line with these observations, IL-2-stimulated NK cells showed robust cytotoxic responses to ES and iPS cells as well as to iPS-cell-derived motoneurons. No significant differences in cytotoxicity levels were observed between KIR/HLA matched and mismatched combinations of NK cells and pluripotent targets. Together, these data indicate that pluripotent stem cells and their neural progeny are targets for NK-cell killing both by failing to sufficiently express ligands for inhibitory receptors and by expression of ligands for activating receptors.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870661","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":"Bone marrow mononuclear cell transplantation promotes bone healing via gap junction-mediated cell-cell interaction.","authors":"Yoshihito Suda, Akihiko Taguchi, Tomoyuki Matsumoto, Yuka Okinaka, Shinya Hayashi, Masanori Tsubosaka, Tomoyuki Kamenaga, Yuichi Kuroda, Naoki Nakano, Yuma Onoi, Shotaro Tachibana, Kensuke Wada, Akira Saito, Takuma Maeda, Shotaro Araki, Kohei Motono, Ryosuke Kuroda","doi":"10.1093/stmcls/sxae090","DOIUrl":"10.1093/stmcls/sxae090","url":null,"abstract":"<p><strong>Aims: </strong>Bone marrow mononuclear cells (BM-MNCs) are a rich source of hematopoietic stem cells that have been widely used in experimental therapies for patients with various diseases, including fractures. Activation of angiogenesis is believed to be one of the major modes of action of BM-MNCs; however, the essential mechanism by which BM-MNCs activate angiogenesis remains elusive. This study aimed to demonstrate that BM-MNCs promote bone healing by enhancing angiogenesis through direct cell-to-cell interactions via gap junctions, in addition to a previously reported method.</p><p><strong>Methods: </strong>Using a murine fracture model, we aimed to elucidate the relationship between gap junction-mediated cell-to-cell interactions and enhanced fracture healing after BM-MNC transplantation. We evaluated the transfer of substances from BM-MNCs to vascular endothelial cells and osteoblasts in the tissues surrounding the fracture site and assessed the effects of BM-MNC transplantation on bone healing, angiogenesis, and osteogenesis.</p><p><strong>Results: </strong>Bone marrow mononuclear cells transferred substances to vascular endothelial cells and osteoblasts in the tissues surrounding the fracture site. Moreover, BM-MNC transplantation promoted bone healing via gap junction-mediated cell-to-cell interactions, accelerating both angiogenesis and osteogenesis.</p><p><strong>Conclusions: </strong>Our findings provide a novel understanding of fracture healing mechanisms and suggest that BM-MNC transplantation enhances bone healing through gap junction-mediated cell-to-cell interactions, contributing to the development of regenerative medicine strategies targeting bone repair.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021456","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}

{"title":"Decoding the epigenetic and transcriptional basis of direct cardiac reprogramming.","authors":"William G Peng, Anteneh Getachew, Yang Zhou","doi":"10.1093/stmcls/sxaf002","DOIUrl":"10.1093/stmcls/sxaf002","url":null,"abstract":"<p><p>Heart disease, particularly resulting from myocardial infarction (MI), continues to be a leading cause of mortality, largely due to the limited regenerative capacity of the human heart. Current therapeutic approaches seek to generate new cardiomyocytes from alternative sources. Direct cardiac reprogramming, which converts fibroblasts into induced cardiomyocytes (iCMs), offers a promising alternative by enabling in situ cardiac regeneration and minimizing tumorigenesis concerns. Here we review recent advancements in the understanding of transcriptional and epigenetic mechanisms underlying cardiac reprogramming, with a focus on key early-stage molecular events, including epigenetic barriers and regulatory mechanisms that facilitate reprogramming. Despite substantial progress, human cardiac fibroblast reprogramming and iCM maturation remain areas for further exploration. We also discuss the combinatorial roles of reprogramming factors in governing transcriptional and epigenetic changes. This review consolidates current knowledge and proposes future directions for promoting the translational potential of cardiac reprogramming techniques.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031834","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":"Patterning effects of FGF17 and cAMP on generation of dopaminergic progenitors for cell replacement therapy in Parkinson's disease.","authors":"Amalie Holm Nygaard, Alrik L Schörling, Zehra Abay-Nørgaard, Erno Hänninen, Yuan Li, Adrian Ramón Santonja, Gaurav Singh Rathore, Alison Salvador, Charlotte Rusimbi, Katrine Bech Lauritzen, Yu Zhang, Agnete Kirkeby","doi":"10.1093/stmcls/sxaf004","DOIUrl":"10.1093/stmcls/sxaf004","url":null,"abstract":"<p><p>Cell replacement therapies using human pluripotent stem cell-derived ventral midbrain (VM) dopaminergic (DA) progenitors are currently in clinical trials for treatment of Parkinson's disease (PD). Recapitulating developmental patterning cues, such as fibroblast growth factor 8 (FGF8), secreted at the midbrain-hindbrain boundary (MHB), is critical for the in vitro production of authentic VM DA progenitors. Here, we explored the application of alternative MHB-secreted FGF-family members, FGF17 and FGF18, for VM DA progenitor patterning. We show that while FGF17 and FGF18 both recapitulated VM DA progenitor patterning events, FGF17 induced expression of key VM DA progenitor markers at higher levels than FGF8 and transplanted FGF17-patterned progenitors fully reversed motor deficits in a rat PD model. Early activation of the cAMP pathway mimicked FGF17-induced patterning, although strong cAMP activation came at the expense of EN1 expression. In summary, we identified FGF17 as a promising alternative FGF candidate for robust VM DA progenitor patterning.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603087","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":"Establishment of vascularized human retinal organoids from induced pluripotent stem cells.","authors":"Satoshi Inagaki, Shinsuke Nakamura, Yoshiki Kuse, Kota Aoshima, Michinori Funato, Masamitsu Shimazawa, Hideaki Hara","doi":"10.1093/stmcls/sxae093","DOIUrl":"10.1093/stmcls/sxae093","url":null,"abstract":"<p><p>Pluripotent stem cell-derived retinal organoids (ROs) have been investigated for applications in regenerative medicine, retinal disease models, and compound safety evaluation. Although the development of 3D organoids has provided novel opportunities for innovation, some unresolved limitations continue to exist in organoid research; the passive diffusion of oxygen and nutrients limits the growth and functional gain of organoids. Vascularization may circumvent these problems because it allows oxygen and nutrients to enter the organoid core. In the present study, we generate the vascularized retinal organoids (vROs) from healthy human induced pluripotent stem cells. vROs are created from ROs by co-culturing them with vascular organoid (VO)-derived vascular endothelial cells/pericytes. The expression of mature neuronal markers is markedly higher in the vROs than in the ROs. When vROs are cultured under diabetic conditions, their size and the number of retinal ganglion cells are significantly decreased. In conclusion, the co-culture of ROs with VO-derived cells enables the production of ROs with vascular-like structures, and the vROs respond to severe diabetic retinopathy conditions. In summary, our findings underscore the potential of vROs as invaluable tools for elucidating disease mechanisms and screening therapeutic interventions for retinal vascular disorders, thereby paving the way for personalized medicine approaches in ophthalmology.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555499","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}

{"title":"Enrichment of spermatogonial stem cells and staging of the testis cycle in a dasyurid marsupial, the fat-tailed dunnart.","authors":"Gerard A Tarulli, Patrick R S Tatt, Rhys Howlett, Sara Ord, Stephen R Frankenberg, Andrew J Pask","doi":"10.1093/stmcls/sxaf007","DOIUrl":"10.1093/stmcls/sxaf007","url":null,"abstract":"<p><p>There is increasing interest in the use of marsupial models in research, for use in next-generation conservation by improving fitness through genetic modification, and in de-extinction efforts. Specifically, this includes dasyurid marsupials such as the Thylacine, Tasmanian devil, quolls, and the small rodent-like dunnarts. Technologies for generating genetically modified Australian marsupials remain to be established. Given the need to advance research in this space, the fat-tailed dunnart (Sminthopsis crassicaudata) is being established as a model for marsupial spermatogonial stem cell isolation, modification, and testicular transplantation. This species is small (60-90 mm body size), polyovulatory (8-12 pups per birth), and can breed in standard rodent facilities when housed in a 12:12 light cycle. To develop the fat-tailed dunnart as a model for next-generation marsupial conservation, this study aimed to enrich dunnart spermatogonial stem cells from whole testis digestions using a fluorescent dye technology and fluorescence-activated cell sorting. This approach is not dependent on antibodies or genetic reporter animals that are limiting factors when performing cell sorting on species separated from humans and mice by large evolutionary timescales. This study also assessed the development of spermatogonia and spermatogenesis in the fat-tailed dunnart, by making the first definition of the cycle of the seminiferous epithelium in any dasyurid. Overall, this is the first detailed study to assess the cycle of dasyurid spermatogenesis and provides a valuable method to enrich marsupial spermatogonial stem cells for cellular, functional, and molecular analysis.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404937","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":"Efficient and rapid generation of neural stem cells by direct conversion of fibroblasts with single microRNAs.","authors":"Yuanyuan Li, Jing Sun, Tingting Xu, Bo Dai, Yuesi Wang","doi":"10.1093/stmcls/sxaf003","DOIUrl":"10.1093/stmcls/sxaf003","url":null,"abstract":"<p><p>Neural stem cells (NSCs) hold great potential in neurodegenerative disease therapy, drug screening, and disease modeling. However, current approaches for induced NSCs (iNSCs) generation from somatic cells are still slow and inefficient. Here we report the establishment of a rapid and efficient method of iNSCs generation from human and mouse fibroblasts by using single microRNAs (miR-302a). These iNSCs exhibited morphological, molecular and functional properties resembling those of adult human and mouse NSCs, respectively. Additionally, human iNSCs can be expanded for more than 20 passages in vitro. Furthermore, miR-302a alone was demonstrated to be sufficient to reprogram both human and mouse fibroblasts into iNSCs. Our results showed a method of direct conversion of autologous fibroblasts with miR-302a into iNSCs, providing a rapid and efficient strategy to generate iNSCs for both basic research and clinical applications.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035484","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}

{"title":"Harnessing the diversity and potential of endogenous skeletal stem cells for musculoskeletal tissue regeneration.","authors":"Kelly C Weldon, Michael T Longaker, Thomas H Ambrosi","doi":"10.1093/stmcls/sxaf006","DOIUrl":"10.1093/stmcls/sxaf006","url":null,"abstract":"<p><p>In our aging society, the degeneration of the musculoskeletal system and adjacent tissues is a growing orthopedic concern. As bones age, they become more fragile, increasing the risk of fractures and injuries. Furthermore, tissues like cartilage accumulate damage, leading to widespread joint issues. Compounding this, the regenerative capacity of these tissues declines with age, exacerbating the consequences of fractures and cartilage deterioration. With rising demand for fracture and cartilage repair, bone-derived stem cells have attracted significant research interest. However, the therapeutic use of stem cells has produced inconsistent results, largely due to ongoing debates and uncertainties regarding the precise identity of the stem cells responsible for musculoskeletal growth, maintenance and repair. This review focuses on the potential to leverage endogenous skeletal stem cells (SSCs)-a well-defined population of stem cells with specific markers, reliable isolation techniques, and functional properties-in bone repair and cartilage regeneration. Understanding SSC behavior in response to injury, including their activation to a functional state, could provide insights into improving treatment outcomes. Techniques like microfracture surgery, which aim to stimulate SSC activity for cartilage repair, are of particular interest. Here, we explore the latest advances in how such interventions may modulate SSC function to enhance bone healing and cartilage regeneration.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404938","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":"Single-cell transcriptome sequencing in synovial joint: insights of new progenitors and targets in joint development and disease.","authors":"Ziqian Wang, Xianni Yang, Haopeng Yu, Songsong Zhu, Ruiye Bi","doi":"10.1093/stmcls/sxaf008","DOIUrl":"10.1093/stmcls/sxaf008","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432052","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}