STEM CELLS最新文献

{"title":"Enforced HCELL expression: empowering \"Step 1\" to optimize the efficacy of mesenchymal stem/stromal cell therapy for stroke and other clinical conditions.","authors":"Robert Sackstein","doi":"10.1093/stmcls/sxae067","DOIUrl":"10.1093/stmcls/sxae067","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1027-1030"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602140","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":"Correction: Immunomodulatory Functions of Adipose Mesenchymal Stromal/Stem Cell Derived From Donors With Type 2 Diabetes and Obesity on CD4 T Cells.","authors":"","doi":"10.1093/stmcls/sxad043","DOIUrl":"10.1093/stmcls/sxad043","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1101"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9626056","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":"The Chondrogenic Potential of the Bovine Tendon Sheath - a Novel Source of Stem Cells for Cartilage Repair.","authors":"Ernst B Hunziker, Naomi Nishii, Nahoko Shintani, Kurt Lippuner, Marius J B Keel, Esther Vögelin","doi":"10.1093/stmcls/sxae071","DOIUrl":"https://doi.org/10.1093/stmcls/sxae071","url":null,"abstract":"<p><p>The human hand is traumatized more frequently than any other bodily part. Trauma and pathological processes (e.g., rheumatoid arthritis, osteoarthritis) commonly implicate the finger joints and specifically damage also the layer of articular cartilage. Endeavors are now being made to surgically repair such cartilage lesions biologically using tissue-engineering approaches that draw on donor cells and/or donor tissues. The tendon sheaths, particularly their inner layers, i.e., the peritendineum, surround the numerous tendons in the hand. The peritendineum is composed of mesenchymal tissue. We hypothesize that this tissue harbors pluripotent mesenchymal stem cells and thus could be used for cartilage repair, irrespective of the donor's age. Using a bovine model (young calves vs. adult cows), the pluripotentiality of the peritendineal stem cells, namely, their osteogenicity, chondrogenicity, and adipogenicity, was investigated by implementing conventional techniques. Subsequently, the chondrogenic potential of the peritendineal tissue itself was analyzed. Its differentiation into cartilage was induced by the application of specific growth factors (members of the TGF-β-superfamily). The characteristics of the tissue formed were evaluated structurally (immuno) histochemically, histomorphometrically, and biochemically (gene expression and protein level). Our data confirm that the bovine peritendineum contains stem cells whose pluripotentiality is independent of donor age. This tissue could also be induced to differentiate into cartilage, likewise, irrespective of the donor's age. Preliminary investigations with adult human peritendineal biopsy material derived from the hand's peritendineal flexor tendon sheaths revealed that this tissue can also be induced to differentiate into cartilage.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826585","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":"Notch Inhibition Enhances Morphological Reprogramming of microRNA-Induced Human Neurons.","authors":"Kyle F Burbach, Shanyun Wu, Andrew S Yoo","doi":"10.1093/stmcls/sxae079","DOIUrl":"10.1093/stmcls/sxae079","url":null,"abstract":"<p><p>The role of Notch signaling in direct neuronal reprogramming remains unknown despite its importance to brain development in vivo. Here, we use microRNA-induced neurons that are directly reprogrammed from human fibroblasts to determine how Notch signaling contributes to neuronal identity. We found that Notch inhibition during the first week of reprogramming was both necessary and sufficient to enhance neurite outgrowth at a later timepoint, indicating an important role in erasure of the original cell identity. Accordingly, transcriptomic analysis showed that the effect of Notch inhibition was likely due to improvements in fibroblast fate erasure and silencing of non-neuronal genes. To this effect, we identify MYLIP, whose downregulation in response to Notch inhibition significantly promoted neurite outgrowth. Moreover, Notch inhibition resulted in cells with neuronal transcriptome signature defined by expressing long genes at a faster rate than the control, demonstrating the effect of accelerated fate erasure on neuronal fate acquisition. Our results demonstrate the antagonistic role of Notch signaling to the pro-neuronal microRNAs 9 and 124 and the benefits of its inhibition to the acquisition of neuronal morphology.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685645","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":"The influence of biomimetic conditions on neurogenic and neuroprotective properties of dedifferentiated fat cells (DFATs).","authors":"Klaudia Radoszkiewicz, Paulina Rybkowska, Magdalena Szymańska, Natalia Ewa Krzesniak, Anna Sarnowska","doi":"10.1093/stmcls/sxae066","DOIUrl":"https://doi.org/10.1093/stmcls/sxae066","url":null,"abstract":"<p><p>In the era of a constantly growing number of reports on the therapeutic properties of dedifferentiated, ontogenetically rejuvenated cells and their use in the treatment of neurological diseases, the optimization of their derivation and long-term culture methods seem to be crucial. One of the solutions is seen in the use of dedifferentiated fat cells (DFATs) which are characterized by a greater homogeneity. Moreover, these cells seem to possess a higher expression of transcriptional factors necessary to maintain pluripotency (STRFs) as well as a greater ability to differentiate in vitro into three embryonic germ layers, and a high proliferative potential in comparison to adipose stem/stromal cells (ASCs). However, the neurogenic and neuroprotective potential of DFATs is still insufficiently understood, hence our research goal is to contribute to our current knowledge of the subject. To recreate the brain's physiological (biomimetic) conditions, the cells were cultured at 5% oxygen concentration. The neural differentiation capacity of DFATs was assessed in the presence of the N21 supplement containing the factors that are typically found in the natural environment of the neural cell niche or in the presence of cerebrospinal fluid (CSF) and under various spatial conditions (microprinting). The neuroprotective properties of DFATs were assessed using the co-culture method with the ischemically damaged nerve tissue.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685665","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":"Trained Mesenchymal Stromal Cell-Based Therapy HXB-319 for Treating Diffuse Alveolar Hemorrhage in a Pristane-induced Murine Model.","authors":"Hulya Bukulmez, Adrienne T Dennis, Jane Reese-Koc, Scott F Sieg, Brian Clagett, Sarah Kleinsorge-Block, Rodrigo Somoza-Palacios, Nora Singer, Mark Chance, Kristin B Highland, Steven N Emancipator","doi":"10.1093/stmcls/sxae078","DOIUrl":"10.1093/stmcls/sxae078","url":null,"abstract":"<p><strong>Introduction: </strong>Mesenchymal stromal cells (MSCs) can modulate immune responses and suppress inflammation in autoimmune diseases. Although their safety has been established in clinical trials, the efficacy of MSCs is inconsistent due to variability in potency among different preparations and limited specificity in targeting mechanisms driving autoimmune diseases.</p><p><strong>Methods: </strong>We utilized High-Dimensional Design of Experiments methodology to identify factor combinations that modulate gene expression by MSCs to mitigate inflammation. This led to a novel MSC-based cell therapy, HXB-319. Its anti-inflammatory properties were validated in vitro by flow cytometry, RT-PCR, and mass spectrophotometry. To evaluate in vivo efficacy, we treated a diffuse alveolar hemorrhage (DAH) mouse model (C57Bl/6). Seven days post-DAH induction with pristane, mice received either MSCs or HXB-319 (2X106 cells, IP). On day 14, peritoneal lavage fluid (PLF) and lung tissue were collected for flow cytometry, histopathological examination and mRNA.</p><p><strong>Results: </strong>HXB-319 increased gene expression levels of anti-inflammatory, angiogenic and anti-fibrotic factors (e.g. TSG-6, VEGF and HGF). KEGG pathway analysis confirmed significant activation of relevant anti-inflammatory, angiogenic, and anti-fibrotic proteins, corroborating RT-PCR results.In the DAH model, HXB-319 significantly reduced lung inflammation and alveolar hemorrhage compared to MSC treated and untreated DAH mice. HXB-319 treatment also significantly decreased neutrophils, plasmacytoid dendritic cells and RORγT cells, and increased FoxP3+ cells in PLF, and reversed alterations in mRNA encoding IL-6, IL-10 and TSG-6 in lung tissue compared to DAH mice.</p><p><strong>Conclusion: </strong>HXB-319 effectively controls inflammation and prevents tissue damage in pristane induced DAH, highlighting its therapeutic potential for autoimmune inflammatory diseases.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666284","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":"A small molecule K-3 promotes PDX1 expression and potentiates the differentiation of pluripotent stem cells into insulin-producing pancreatic β cells.","authors":"Tatsuya Yano, Yukihiro Shimaya, Takayuki Enomoto, Toshihiro Kiho, Satoshi Komoriya, Ryutaro Nakashima, Nobuaki Shiraki, Shoen Kume","doi":"10.1093/stmcls/sxae075","DOIUrl":"https://doi.org/10.1093/stmcls/sxae075","url":null,"abstract":"<p><p>Insulin-producing pancreatic β-like cells derived from human pluripotent stem cells (PSCs) are anticipated as a novel cell source for cell replacement therapy for diabetes patients. Here, we describe the identification of small molecule compounds that promote the differentiation of the PSCs into insulin-producing cells by high throughput screening with a chemical library composed of 55,000 compounds. The initial hit compound K-1 and one derivative K-3 increased the proportion of PSC-derived insulin-positive endocrine cells and their glucose-stimulated insulin secretory (GSIS) functions. K-3 preferentially acts on stage 3 pancreatic progenitor cells and increases the population expressing high levels of PDX1. As a result, the ratios of the PSC-derived PDX1 / NKX6.1 double-positive endocrine progenitor and INS / NKX6.1 double-positive mono-hormonal endocrine cells were increased. K-3 enhances the expression of functional pancreatic β cell markers and affects biological processes concerning organ development. K-3 also increased the yield of endocrine cells at the end of stage 5. The novel compound is a beneficial new tool for efficiently generating PSC-derived insulin-producing cells with high functionality and differentiation efficiency.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646502","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":"Microglia in the spinal cord stem cell niche regulate neural precursor cell proliferation via soluble CD40 in response to myelin basic protein.","authors":"Nishanth Lakshman, Filip Stojic, Cindi M Morshead","doi":"10.1093/stmcls/sxae076","DOIUrl":"https://doi.org/10.1093/stmcls/sxae076","url":null,"abstract":"<p><p>Neural stem cells (NSCs) are found along the neuraxis of the developing and mature central nervous system. They are found in defined niches that have been shown to regulate NSC behaviour in a regionally distinct manner. Specifically, previous research has shown that myelin basic protein (MBP), when presented in the spinal cord niche, inhibits NSC proliferation and oligodendrogenesis. Herein, we investigate the cell-based mechanism(s) underlying this spinal-cord niche derived MBP-mediated inhibition. We used reporter mice to sort for subpopulations of cells and found that spinal cord niche derived microglia release a soluble factor in response to MBP that is responsible for NSC inhibition. Microglia, but not other niche cells, release soluble CD40/TNFRSF5 (sCD40) in the presence of MBP which may indirectly reduce activation of transmembrane CD40/TNFRSF5 receptor on both spinal cord and brain NSCs. This is consistent with sCD40 binding to CD40 ligand (CD40L) thereby preventing CD40 receptor binding on NSCs and inhibiting NSC proliferation. The identification of the cell-based mechanism that regulates NSC behaviour in response to MBP, which is dysregulated in injury/disease, provides insight into a potential target for strategies to enhance neural repair through endogenous stem cell activation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643574","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":"Therapeutic potential of stem cell-derived extracellular vesicles in neurodegenerative diseases associated with cognitive decline.","authors":"Matteo Spinelli, Salvatore Fusco, Claudio Grassi","doi":"10.1093/stmcls/sxae074","DOIUrl":"https://doi.org/10.1093/stmcls/sxae074","url":null,"abstract":"<p><p>In the central nervous system, cell-to-cell interaction is essential for brain plasticity and repair, and its alteration is critically involved in the development of neurodegenerative diseases. Neural stem cells are a plentiful source of biological signals promoting neuroplasticity and the maintenance of cognitive functions. Extracellular vesicles (EVs) represent an additional strategy for cells to release signals in the surrounding cellular environment or to exchange information among both neighboring and distant cells. In the last years, rising attention has been devoted to the ability of stem cell (SC)-derived EVs to counteract inflammatory and degenerative brain disorders taking advantage of their immunomodulatory capacities and regenerative potential. Here, we review the role of adult neurogenesis impairment in the cognitive decline associated with neurodegenerative diseases and describe the beneficial effects of SC-derived EVs on brain plasticity and repair also discussing the advantages of SC-derived EV administration versus SC transplantation in the treatment of neurodegenerative disorders.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613252","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":"Rapid Disease Progression of Myelodysplastic Syndrome is Reflected in Transcriptomic and Functional Abnormalities of Bone Marrow MSCs.","authors":"Hein Than, Xiubo Fan, Alice M S Cheung, William Y K Hwang, Zhiyong Poon","doi":"10.1093/stmcls/sxae073","DOIUrl":"https://doi.org/10.1093/stmcls/sxae073","url":null,"abstract":"<p><p>Bone marrow (BM) mesenchymal stromal cells (MSCs) are important regulators of hematopoietic stem and progenitor cells (HSPCs). When transformed to a dysplastic phenotype, MSCs contribute to hematopoietic diseases such as myelodysplastic syndromes (MDS), but it remains unclear if there are specific properties in MDS-MSCs that contribute to the disease course. To understand this, we investigated MDS-MSCs from fast (MDSfast) vs slow (MDSslow) progressing disease groups and discovered differences between these groups. MDSfast-MSCs secrete more inflammatory factors, support myeloid-skewed differentiation of HSPCs, and importantly, show poorer response to hypomethylation as a key differentiator in GSEA analysis. When exposed to long-term in vivo stimulation with primary MDSfast-MSCs-based scaffolds, healthy donor (HD) HSPCs show elevated NF-κB expression, similar to leukemic HSPCs in MDS. Those \"MDSfast-MSCs-primed\" HD-HSPCs continue to show enhanced engraftment rates in secondary MDS-MSC-based scaffolds, providing evidence for the microenvironmental selection pressures in MDS towards leukemic HSPCs. Together, our data point towards a degree of co-development between MSCs and HSPCs during the progression of MDS, where changes in MDS-MSCs take place mainly at the transcriptomic and functional levels. These unique differences in MDS-MSCs can be utilized to improve disease prognostication and implement targeted therapy for unmet clinical needs.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613249","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}