Stem cells and development最新文献

{"title":"Human Adipose-derived Mesenchymal Stem Cells Colonize and Promote Healing of Leprosy Ulcer by Inducing Neuro-vascularization.","authors":"Chaojiang Cheng, Yi Zhang, Haiqing Jiang, Ying Shi, Tianping Xue, Xinfeng Wu, Hongsheng Wang","doi":"10.1089/scd.2024.0017","DOIUrl":"https://doi.org/10.1089/scd.2024.0017","url":null,"abstract":"Leprosy ulcer is a chronic and recurrent disease resulting from nerve injury. While existing treatments partially facilitate ulcer healing, they exhibit limited ability to address localized nerve repair, leading to a risk of recurrence. Moreover, there is a dearth of animal models to evaluate the preclinical efficacy and safety of novel therapeutic approaches. Over the years, adipose-derived mesenchymal stem cells have been extensively employed in regenerative medicine as an optimal cell therapy source for fostering skin ulcer healing. They have also demonstrated the capacity to enhance nerve regeneration in vitro experiments and clinical trials. In this study, we established a NU/NU mouse foot pad leprosy ulcer model, transplanted human adipose-derived stem cells (hADSCs) into leprosy ulcers via local injection, and conducted subsequent follow-up. Our findings revealed that hADSCs persisted in the leprosy ulcer and facilitated healing process. In this respect, gross observation and histological analysis revealed increased granular formation, collagen synthesis, and re-epithelialization in the local ulcer area. RNA-Seq data revealed that the upregulated differential genes resulting from the transplantation intervention were not only enriched in pathways related to re-epithelialization and collagen synthesis but also contributed to local nerve regeneration. Furthermore, immunofluorescence assays revealed the increased expression of angiogenesis markers CD31 and VEGFa, cell proliferation markers Ki67 and TGF-β, and nerve regeneration markers β3-tubulin, SOX10, NGF, and NT-3. These results underscore the potential of hADSCs in promoting the healing of leprosy ulcers and offer valuable preclinical data for their prospective clinical application.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140653197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FoxO3 regulates mouse bone mesenchymal stem cell fate and bone-fat balance during skeletal aging.","authors":"Wei Yu, Min-Ji Tong, Guo-Hao Wu, Tian-Le Ma, Chuan-Dong Cai, Li-Peng Wang, Ying-Kai Zhang, Jin-Lun Gu, Zuoqin Yan","doi":"10.1089/scd.2024.0055","DOIUrl":"https://doi.org/10.1089/scd.2024.0055","url":null,"abstract":"Age-related osteoporosis is characterized by an imbalance between osteogenic and adipogenic differentiation in bone mesenchymal stem cells (BMSCs). Forkhead box O 3 (FoxO3) transcription factors is involved in lifespan and cell differentiation. In this study, we explore whether FoxO3 regulates age-related bone loss and marrow fat accumulation. The expression levels of FoxO3 in BMSCs during aging were detected in vivo and in vitro. To explore the role of FoxO3 in osteogenic and adipogenic differentiation, primary BMSCs were isolated from young and aged mice. FoxO3 expression was modulated by adenoviral vector transfection. The role of FoxO3 in bone-fat balance was evaluated by alizarin red S staining, oil red O staining, quantitative reverse transcription-PCR (qRT-PCR), western blot (WB) and histological analysis. Age-related bone loss and fat deposit are associated with downregulation of FoxO3. Overexpression of FoxO3 alleviated age-related bone loss and marrow fat accumulation in aged mice. Mechanistically, FoxO3 reduced adipogenesis and enhanced osteogenesis of BMSCs via downregulation of PPAR-γ and Notch signaling respectively. In conclusion, FoxO3 is an essential factor controlling the fate of BMSCs, and is a potential target for prevention of age-related osteoporosis.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140655197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: The Essence of Quiescence, by Peter Quesenberry et al., Stem Cells Dev 2024;33(7-8):149-152; doi: 10.1089/scd.2024.0032.","authors":"","doi":"10.1089/scd.2024.0032.correx","DOIUrl":"https://doi.org/10.1089/scd.2024.0032.correx","url":null,"abstract":"","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140693109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key Roles of Gli1 and Ihh Signaling in Craniofacial Development.","authors":"Qi Sun, Jie Huang, Jingjun Tian, Changhai Lv, Yanhong Li, Siyuan Yu, Juan Liu, Jun Zhang","doi":"10.1089/scd.2024.0036","DOIUrl":"https://doi.org/10.1089/scd.2024.0036","url":null,"abstract":"The Hedgehog (Hh) signaling pathway orchestrates its influence through a dynamic interplay of Hh proteins, the cell surface receptor Ptch1, Smo, and Gli transcription factors, contributing to a myriad of developmental events. Indian Hedgehog (Ihh) and Gli zinc finger transcription factor 1 (Gli1) play crucial roles in developmental regulation within the Hh signaling pathway. Ihh regulates chondrocyte proliferation, differentiation, and bone formation, impacting the development of cranial bones, cartilage, and the temporomandibular joint (TMJ). Losing Ihh results in cranial bone malformation, decreased ossification, and affects the formation of cranial base cartilage unions, TMJ condyles, and joint discs. Gli1 is predominantly expressed during early craniofacial development, and Gli1+ cells are identified as the primary mesenchymal stem cells (MSCs) for craniofacial bones, crucial for cell differentiation and morphogenesis. Additionally, a complex mutual regulatory mechanism exists between Gli1 and Ihh, ensuring the normal function of the Hh signaling pathway by directly or indirectly regulating each other's expression levels. And the interaction between Ihh and Gli1 significantly impacts the normal development of craniofacial tissues.This review summarizes the pivotal roles of Gli1 and Ihh in the intricate landscape of mammalian craniofacial development, and outlines the molecular regulatory mechanisms and intricate interactions governing the growth of bone and cartilage exhibited by Gli1 and Ihh, which Provides new insights into potential therapeutic strategies for related diseases or researches of tissue regeneration.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140697791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low initial cell density promotes the differentiation and maturation of human pluripotent stem cells into erythrocytes.","authors":"Liqing Liang, Lei Xu, Qian Dong, Jing Zhang, M. Qu, Xin Yuan, Q. Zeng, Huilin Li, Bowen Zhang, Chao Wang, Tao Fan, Li-juan He, Wen Yue, Xiaoyan Xie, Xuetao Pei","doi":"10.1089/scd.2023.0204","DOIUrl":"https://doi.org/10.1089/scd.2023.0204","url":null,"abstract":"Human pluripotent stem cell (hPSC)-derived red blood cells (RBCs) possess great potential for compensating shortages in transfusion medicine. For better RBC generation from hPSCs, we compared the cell seeding density in the embryoid body formation-based hPSC induction protocol. In the selection of low- and high-density inoculation conditions, we found that low-density culture performed better in the final RBC product with more cell output and increased average cellular hemoglobin content. An elaborate study using flow cytometry demonstrated that low inoculation density promoted endothelial-to-hematopoietic transition, followed by improved hematopoietic progenitor formation and erythrocyte generation. The improved transformation from glycolysis to mitochondrial oxidation and reduced apoptosis might be responsible for this effect. Hints from RNA sequencing suggested that molecules involved in microenvironment interaction and metabolic regulation might respond for the different developmental potential. The possible mediators between outer message and intracellular response could be the nutrition sensors FOXO, PRKAA1 (AMPK) and MTOR genes. It is possible that low inoculation density triggered metabolic regulation signals, promoted mitochondrial oxidation, and resulted in enhanced cell amplification and hematopoietic differentiation. The low cell culture density will improve RBC generation from human PSCs.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140706736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: The Benefits of Stem Cell Biology and TissueEngineering in Low-Earth Orbit, by Madelyn Arzt et al. Stem Cells and Development 2024;33(5-6):143-147; doi: 10.1089/scd.2023.0291.","authors":"","doi":"10.1089/scd.2023.0291.correx","DOIUrl":"https://doi.org/10.1089/scd.2023.0291.correx","url":null,"abstract":"","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140715163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes derived from mesenchymal stem cells increase the viability of damaged endometrial cells via the miR-99b-5p/PCSK9 axis.","authors":"Lifei Li, J. An, Yan Wang, Lin Liu, Yiqing Wang, Xuehong Zhang","doi":"10.1089/scd.2023.0259","DOIUrl":"https://doi.org/10.1089/scd.2023.0259","url":null,"abstract":"To investigate whether exosomes derived from bone marrow mesenchymal stem cells repair damaged endometrial stromal cells through the miR-99b-5p/PCSK9 axis. Exosomes derived from BMSCs (BMSC-exos) were isolated by ultracentrifugation and characterized using transmission electron microscopy and nanoflow cytometry. A mifepristone-induced EnSC injury model was established in vitro, and the uptake of BMSC-exos assessed. EnSCs were divided into three groups: the normal group (ctrl), EnSC injury group (model) and BMSC-exo treatment group. The effects of BMSC-exos on EnSC proliferation, apoptosis, and vascular endothelial growth factor (VEGF) expression were assessed by coculturing MSC-exos with endometrial cells. Furthermore, high-throughput sequencing was used to identify differentially expressed genes (DEGs). Through bioinformatics analysis, RT‒qPCR, western blotting, the CCK8 assay, immunohistochemistry and dual luciferase experiments, the potential mechanism by which BMSC-exos derived miRNAs repair EnSC injury was studied. BMSC-exos expressed the marker proteins CD9 and CD63. Laser confocal microscopy showed that BMSC-exos could enter damaged EnSCs. In the BMSC-exos-EnSC coculture group compared with the model group, BMSC-exos significantly increased the proliferation of damaged EnSC and inhibited cell apoptosis in a dose-dependent manner. The expression levels of Caspase-3, Caspase-9, Bax and VEGF mRNA were significantly downregulated in the BMSC-exos-EnSC coculture group, while Bcl-2 expression was upregulated. We identified 28 overlapping DEGs between the model and ctrl groups, and between the BMSC-exo and model groups. Transfection with miR-99b-5p mimics significantly decreased PCSK9 gene expression and inhibited the expression of the autophagy related proteins Beclin-1 and LC3-II/I and apoptosis, thereby promoting EnSC proliferation. Transfection with a miR-99b-5p inhibitor showed the opposite effects. Beclin-1, LC3-II/I and PCSK9 expression in the thin endometrium was significantly increased. miR-99b-5p promoted cell proliferation by targeting PCSK9. BMSC-exos promoted endometrial proliferation, and miR-99b-5p inhibited cell apoptosis and promoted EnSC proliferation by targeting PCSK9, providing a new target for the treatment of thin endometrium.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140742460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Slice Culture System for Successional Dental Lamina in Diphyodont Mammals.","authors":"Qiong Li, Xiaoyu Lin, Ran Zhang, Jiangyi Wang, Jinsong Wang, Chunmei Zhang, Songlin Wang, Xiaoshan Wu","doi":"10.1089/scd.2024.0044","DOIUrl":"https://doi.org/10.1089/scd.2024.0044","url":null,"abstract":"Replacement teeth develop from the successional dental lamina (SDL). Understanding how SDL transitions from quiescence to initiation is crucial for preserving dental lamina stem cells in the jawbone microenvironment and for complete tooth regeneration. Miniature pigs are good models for studying human tooth replacement because of their similarities to humans. However, the molecular mechanisms and cellular composition that initiate SDL development remain unclear. One possible reason for this is the limitations of the current methods for culturing SDL in vitro, such as the inability to directly observe tooth morphological changes during culture and low tissue viability. This study aimed to improve the in vitro culture method for SDL. Using a McIlwain Tissue Chopper, we obtained mandibular slices containing deciduous canine and SDL of permanent canine. The slices were approximately 500 μm thick and were cultured on a Transwell membrane supported with metal grids over medium. The SDL developed into the bud stage on the 2nd day and entered the cap stage on the 5th day in vitro. The expression of proliferation markers, cell death markers, and key odontogenetic genes in vitro was similar to that observed in vivo. In conclusion, we successfully applied a slice culture system to the SDL of miniature pigs. This slice culture method allowed us to directly visualize SDL initiation and further elucidate the molecular mechanisms underlying the initiation of permanent tooth development.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140742018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of Plant-made Fibroblast Growth Factor for Human Pluripotent Stem Cells","authors":"Junjing Jia, Whitney Wilson, Mahmudul Hasan, Asuka Nishimura, Hayuma Otsuka, Kazuaki Ohara, Hiroshi Okawa, Karen McDonald, Somen Nandi, John Albeck, Raymond Rodriguez, Ping Zhou, Jan A Nolta","doi":"10.1089/scd.2023.0135","DOIUrl":"https://doi.org/10.1089/scd.2023.0135","url":null,"abstract":"","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138587850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stromal Cells Regulate M1/M2 Macrophage Polarization in Mice with Immune Thrombocytopenia.","authors":"Ziyang Liang, Guoyang Zhang, GuangTing Gan, Xiaoyan Liu, Hongyun Liu, Danian Nie, Liping Ma","doi":"10.1089/scd.2023.0154","DOIUrl":"10.1089/scd.2023.0154","url":null,"abstract":"<p><p>Mesenchymal stromal cells have shown promising effects in the treatment of immune thrombocytopenia. However, the underlying mechanisms are not fully understood. In this study, we investigated the therapeutic effects of human bone marrow mesenchymal stromal cells (hBMSCs) and analyzed their unique role in regulating the M1/M2 macrophage ratio. We established a passive immune thrombocytopenia (ITP) mouse model and showed that there was a significant M1/M2 imbalance in ITP model mice by assessing the M1/M2 ratios in the liver, spleen, and bone marrow; we observed excessive activation of M1 cells and decreased M2 cell numbers in vivo. We have shown that systemic infusion of hBMSCs effectively elevated platelet levels after disease onset. Further analysis revealed that hBMSCs treatment significantly suppressed the number of proinflammatory M1 macrophages and enhanced the number of anti-inflammatory M2 macrophages; in addition, the levels of proinflammatory factors, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), were significantly decreased in vivo, while the levels of the anti-inflammatory factor interleukin-10 (IL-10) were increased. In conclusion, our data suggest that hBMSCs treatment can effectively increase platelet counts, and the mechanism is related to the induction of macrophage polarization toward the anti-inflammatory M2 phenotype and the decrease in proinflammatory cytokine production, which together ameliorate innate immune disorders.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}