Stem cells and development最新文献

{"title":"Donor-Recipient Chimeric Cells (DRCC) Transplantation as the Bridging Therapy for Mitigating Total Body Irradiation-Induced Injury.","authors":"Maria Siemionow, Krzysztof Bieda, Katarzyna Stawarz, Malgorzata Cyran, Lucile Chambily, Krzysztof Kusza","doi":"10.1089/scd.2024.0068","DOIUrl":"https://doi.org/10.1089/scd.2024.0068","url":null,"abstract":"In recent years, cell-based therapies have emerged as a promising approach for mitigating radiation-induced injury. Acute radiation syndrome (ARS) results from exposure to high doses of radiation over a short time period. This study aimed to compare the efficacy of donor-recipient chimeric cell (DRCC) therapy in mitigating ARS induced by a total body irradiation (TBI) dose of 10 gray (Gy). Thirty irradiated Lewis rats were employed as ARS models to assess the efficacy of systemic-intraosseous transplantation of different cellular therapies in five experimental groups (n=6/group): saline control, isogeneic bone marrow transplantation (isoBMT), allogeneic BMT (alloBMT), DRCC, and alloBMT+DRCC. DRCC were created by polyethylene glycol-mediated fusion of bone marrow cells from 24 ACI (RT1a) and 24 Lewis (RT11) rat donors. The creation of DRCC and chimeric state were confirmed by flow cytometry (FC) and confocal microscopy (CM). Recovery of blood parameters was evaluated via complete blood count analysis. GvHD (graft-versus-host disease) signs were assessed clinically and histopathologically using kidney, skin, and small intestine biopsies. FC and CM confirmed the fusion feasibility and the chimeric state of DRCC. A 100% mortality rate was observed in the saline control group, whereas a 100% survival was recorded following DRCC transplantation, correlating with significant recovery of peripheral blood parameters. Additionally, no clinical or histopathological signs of GvHD were observed after DRCC and alloBMT+DRCC transplantation. These findings confirm efficacy of DRCC in mitigating GvHD, promoting hematopoietic recovery, and increasing animal survival following TBI-induced ARS.​​ Moreover, tolerogenic and immunomodulatory properties of DRCC therapy support its feasibility for clinical applications. Therefore, this study introduces DRCC as an innovative bridging therapy for alleviating the acute effects of TBI, with broad implications for stem cell research and regenerative medicine.","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":"55 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140971119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor-Recipient Chimeric Cells (DRCC) Transplantation as the Bridging Therapy for Mitigating Total Body Irradiation-Induced Injury.","authors":"Maria Siemionow, Krzysztof Bieda, Katarzyna Stawarz, Malgorzata Cyran, Lucile Chambily, Krzysztof Kusza","doi":"10.1089/scd.2024.0068","DOIUrl":"https://doi.org/10.1089/scd.2024.0068","url":null,"abstract":"<p><p>In recent years, cell-based therapies have emerged as a promising approach for mitigating radiation-induced injury. Acute radiation syndrome (ARS) results from exposure to high doses of radiation over a short time period. This study aimed to compare the efficacy of donor-recipient chimeric cell (DRCC) therapy in mitigating ARS induced by a total body irradiation (TBI) dose of 10 gray (Gy). Thirty irradiated Lewis rats were employed as ARS models to assess the efficacy of systemic-intraosseous transplantation of different cellular therapies in five experimental groups (n=6/group): saline control, isogeneic bone marrow transplantation (isoBMT), allogeneic BMT (alloBMT), DRCC, and alloBMT+DRCC. DRCC were created by polyethylene glycol-mediated fusion of bone marrow cells from 24 ACI (RT1a) and 24 Lewis (RT11) rat donors. The creation of DRCC and chimeric state were confirmed by flow cytometry (FC) and confocal microscopy (CM). Recovery of blood parameters was evaluated via complete blood count analysis. GvHD (graft-versus-host disease) signs were assessed clinically and histopathologically using kidney, skin, and small intestine biopsies. FC and CM confirmed the fusion feasibility and the chimeric state of DRCC. A 100% mortality rate was observed in the saline control group, whereas a 100% survival was recorded following DRCC transplantation, correlating with significant recovery of peripheral blood parameters. Additionally, no clinical or histopathological signs of GvHD were observed after DRCC and alloBMT+DRCC transplantation. These findings confirm efficacy of DRCC in mitigating GvHD, promoting hematopoietic recovery, and increasing animal survival following TBI-induced ARS.​​ Moreover, tolerogenic and immunomodulatory properties of DRCC therapy support its feasibility for clinical applications. Therefore, this study introduces DRCC as an innovative bridging therapy for alleviating the acute effects of TBI, with broad implications for stem cell research and regenerative medicine.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival and Functional Integration of Human Embryonic Stem Cell-Derived Retinal Organoids After Shipping and Transplantation into Retinal Degeneration Rats.","authors":"Bin Lin, Ratnesh K Singh, Magdalene J Seiler, Igor O Nasonkin","doi":"10.1089/scd.2023.0257","DOIUrl":"10.1089/scd.2023.0257","url":null,"abstract":"<p><p>Because derivation of retinal organoids (ROs) and transplantation are frequently split between geographically distant locations, we developed a special shipping device and protocol capable of the organoids' delivery to any location. Human embryonic stem cell (hESC)-derived ROs were differentiated from the hESC line H1 (WA01), shipped overnight to another location, and then transplanted into the subretinal space of blind immunodeficient retinal degeneration (RD) rats. Development of transplants was monitored by spectral-domain optical coherence tomography. Visual function was accessed by optokinetic tests and superior colliculus (SC) electrophysiology. Cryostat sections through transplants were stained with hematoxylin and eosin; or processed for immunohistochemistry to label human donor cells, retinal cell types, and synaptic markers. After transplantation, ROs integrated into the host RD retina, formed functional photoreceptors, and improved vision in rats with advanced RD. The survival and vision improvement are comparable with our previous results of hESC-ROs without a long-distance delivery. Furthermore, for the first time in the stem cell transplantation field, we demonstrated that the response heatmap on the SC showed a similar shape to the location of the transplant in the host retina, which suggested the point-to-point projection of the transplant from the retina to SC. In conclusion, our results showed that using our special device and protocol, the hESC-derived ROs can be shipped over long distance and are capable of survival and visual improvement after transplantation into the RD rats. Our data provide a proof-of-concept for stem cell replacement as a therapy for RD patients.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"201-213"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biodistribution and Safety of Human Multi-Chimeric Cells After Systemic Intraosseous and Intravenous Administration in the Experimental Mouse Model.","authors":"Maria Siemionow, Lucile Chambily, Joanna Cwykiel","doi":"10.1089/scd.2024.0007","DOIUrl":"10.1089/scd.2024.0007","url":null,"abstract":"<p><p>Cellular therapies provide promising options for inducing tolerance in transplantation of solid organs, bone marrow, and vascularized composite allografts. However, novel tolerance-inducing protocols remain limited, despite extensive research. We previously introduced and characterized a human multi-chimeric cell (HMCC) line, created through ex vivo fusion of human umbilical cord blood (UCB) cells derived from three unrelated donors. In this study, we assessed in vivo biodistribution and safety of HMCCs in the NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ NOD scid gamma (NSG) mouse model. Twenty-four NSG mice were randomly assigned to four groups (<i>n</i> = 6/group) and received intraosseous (IO.) or intravenous (IV.) injections of 0.6 × 10⁶ donor UCB cells or fused HMCC: Group 1-UCB (IO.), Group 2-UCB (IV.), Group 3-HMCC (IO.), and Group 4-HMCC (IV.). Hematopoietic phenotype maintenance and presence of human leukocyte antigens (HLA), class I antigens, in the selected lymphoid and nonlymphoid organs were assessed by flow cytometry. Weekly evaluation and magnetic resonance imaging (MRI) assessed HMCC safety. Comparative analysis of delivery routes revealed significant differences in HLA class I percentages for IO.: 1.83% ± 0.79%, versus IV. delivery: 0.04% ± 0.01%, <i>P</i> < 0.01, and hematopoietic stem cell marker percentages of CD3 (IO.: 1.41% ± 0.04%, vs. IV.: 0.07% ± 0.01%, <i>P</i> < 0.05) and CD4 (IO.: 2.74% ± 0.31%, vs. IV.: 0.59% ± 0.11%, <i>P</i> < 0.01). Biodistribution analysis after IO. delivery confirmed HMCC presence in lymphoid organs and negligible presence in nonlymphoid organs, except for lung (IO.: 0.19% ± 0.06%, vs. IV.: 6.33% ± 0.56%, <i>P</i> < 0.0001). No evidence of tumorigenesis was observed by MRI at 90 days following IO. and IV. administration of HMCC. This study confirmed biodistribution and safety of HMCC therapy in the NSG mouse model, both following IO. and IV. administration. However, IO. delivery route confirmed higher efficacy of engraftment and safety profile, introducing HMCCs as a novel cell-based therapeutic approach with promising clinical applications in solid organ, bone marrow, and vascularized composite allotransplantation transplantation.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"214-227"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Fibrillin-2 on Differentiation into Periodontal Ligament Stem Cell-Like Cells Derived from Human-Induced Pluripotent Stem Cells.","authors":"Sayuri Hamano, Diaki Yamashita, Daigaku Hasegawa, Hideki Sugii, Tomohiro Itoyama, Hidefumi Maeda","doi":"10.1089/scd.2024.0013","DOIUrl":"10.1089/scd.2024.0013","url":null,"abstract":"<p><p>Periodontal tissue regeneration is important for preserving teeth. Periodontal ligament stem cells (PDLSCs) are useful in periodontal tissue regeneration; however, tooth extraction is required to obtain these cells. Therefore, we focused on induced pluripotent stem (iPS) cells and established a method to obtain PDLSC-like cells from iPS cells. Specifically, we first differentiated iPS cells into neural crest-like cells (iNCs). Next, we obtained PDLSC-like cells (iPDLSCs) by culturing iNCs on extracellular matrix (ECM) derived from human primary periodontal ligament cells (HPDLCs). This differentiation method suggested that ECM derived from HPDLCs is important for iPDLSC differentiation. Thus, we aimed to identify the PDLSC-inducing factor present in HPDLC-derived ECM in this study. We first performed comprehensive analyses of HPDLC genes and identified fibrillin-2 (<i>FBN2</i>), an ECM-related factor. Furthermore, to clarify the effect of FBN2 on iPDLSC differentiation, we cultured iNCs using ECM derived from HPDLCs with <i>FBN2</i> knocked down. As a result, expression of PDL-related markers was reduced in iNCs cultured on ECM derived from HPDLCs transfected with FBN2 siRNA (iNC-siFBN2) compared with iPDLSCs. Furthermore, the expression of CD105 (a mesenchymal stem cell marker), proliferation ability, and multipotency of iNC-siFBN2 were lower compared with iPDLSCs. Next, we cultured iNCs on FBN2 recombinant protein; however, expression of PDL-related markers did not increase compared with iPDLSC. The present results suggest the critical involvement of FBN2 in inducing iPDLSCs from iNCs when in fact it does not promote iPDLSC differantiation. Therefore, we need to elucidate the entire HPDLC-ECMs, responsible for iPDLSCs induction.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"228-238"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Essence of Quiescence.","authors":"Peter Quesenberry, Mark Dooner, Mandy Pereira, Nathalie Oulhen, Sicheng Wen","doi":"10.1089/scd.2024.0032","DOIUrl":"10.1089/scd.2024.0032","url":null,"abstract":"<p><p>Historically hematopoietic stem cells are believed to be predominantly dormant but could be induced into active cell cycle under specific conditions. This review, coupled with years of research from our laboratory, challenges this belief by demonstrating a significant portion of hematopoietic stem cells are actively cycling rather than quiescent. This addresses a major heuristic error in the understanding of hematopoietic stem cells that has shaped this field for decades. By evaluating the cycle status of engraftable hematopoietic stem cells in whole unseparated bone marrow, we demonstrated that a significant portion of these cells are actively cycling, and further confirmed by tritiated thymidine suicide and bromodeoxyuridine labeling assays. Moreover, by analyzing both whole unseparated bone marrow and purified lineage-negative hematopoietic stem cells in murine models, our findings indicate that lineage-positive cells, usually discarded during purification, actually contain actively cycling stem cells. Taken together, our findings highlight that hematopoietic stem cells are characterized as actively cycling and expressing differentiation epitopes. This corrects a basic mistake in stem cell biology. Furthermore, these findings provide valuable insights for a better understanding of the actively cycling hematopoietic stem cells in the field of stem cell biology.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"149-152"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11036883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiation of Human-induced Pluripotent Stem Cell-derived Dental Stem Cells through Epithelial-Mesenchymal Interaction.","authors":"Ji-Hye Kim, Jihye Yang, Min-Gi Ki, Dae Hyun Jeon, Jae-Won Kim, Mi Jang, Gene Lee","doi":"10.1089/scd.2023.0220","DOIUrl":"10.1089/scd.2023.0220","url":null,"abstract":"<p><p>Research on tooth regeneration using human-induced pluripotent stem cells (hiPSCs) is valuable for autologous dental regeneration. Acquiring mesenchymal and epithelial cells as a resource for dental regeneration is necessary because mesenchymal-epithelial interactions play an essential role in dental development. We reported the establishment of hiPSCs-derived dental epithelial-like cell (EPI-iPSCs), but hiPSCs-derived dental mesenchymal stem cells (MSCs) have not yet been reported. This study was conducted to establish hiPSCs-derived MSCs and to differentiate them into dental cells with EPI-iPSCs. Considering that dental MSCs are derived from the neural crest, hiPSCs were induced to differentiate into MSCs through neural crest formation to acquire the properties of dental MSCs. To differentiate hiPSCs into MSCs through neural crest formation, established hiPSCs were cultured and differentiated with PA6 stromal cells and differentiated hiPSCs formed neurospheres on ultralow-attachment plates. Neurospheres were differentiated into MSCs in serum-supplemented medium. Neural crest-mediated MSCs (NC-MSCs) continuously showed typical MSC morphology and expressed MSC markers. After 8 days of odontogenic induction, the expression levels of odontogenic/mineralization-related genes and dentin sialophosphoprotein (DSPP) proteins were increased in the NC-MSCs alone group in the absence of coculturing with dental epithelial cells. The NC-MSCs and EPI-iPSCs coculture groups showed high expression levels of amelogenesis/odontogenic/mineralization-related genes and DSPP proteins. Furthermore, the NC-MSCs and EPI-iPSCs coculture group yielded calcium deposits earlier than the NC-MSCs alone group. These results indicated that established NC-MSCs from hiPSCs have dental differentiation capacity with dental epithelial cells. In addition, it was confirmed that hiPSCs-derived dental stem cells could be a novel cell source for autologous dental regeneration.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"189-199"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139748009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Evaluation of Safety and Efficacy of a Central Current Good Manufacturing Practices Laboratory Produced Autologous Adipose-Derived Stromal Vascular Fraction Cell Therapy Product for the Treatment of Knee Osteoarthritis.","authors":"Christopher J Rogers, Robert Harman, Mitchell B Sheinkop, Peter Hanson, Mary A Ambach, Tal David, Rahul Desai, Steven Sampson, Danielle Aufierro, Jay Bowen, Gerard Malanga","doi":"10.1089/scd.2024.0008","DOIUrl":"10.1089/scd.2024.0008","url":null,"abstract":"<p><p>Knee osteoarthritis (KOA) is a prevalent condition characterized by the progressive deterioration of the entire joint and has emerged as a prominent contributor to disability on a global scale. The nature of the disease and its impact on joint function significantly limit mobility and daily activities, highlighting its substantial influence on patients' overall well-being. Stromal vascular fraction (SVF) is a heterogenous, autologous cell product, containing mesenchymal stem cells, derived from the patient's subcutaneous adipose tissue with demonstrated safety and efficacy in the treatment of KOA patients. We conducted a single-arm, open-label, multisite, FDA approved clinical study in Kellgren-Lawrence severity grade 2-4 KOA patients. The cellular product was manufactured from patient-specific lipoaspirate in a centrally located FDA-compliant manufacturing facility. Twenty-nine subjects were treated with a quality tested single intra-articular injection of GMP manufactured SVF. Adverse events, laboratory values, vital signs, and physical examination findings were monitored during the study period. Robust tolerability, without any substantial safety issues, was demonstrated. Knee pain and function, assessed through the Knee Injury and Osteoarthritis Outcome Score (KOOS), demonstrated notable improvements. These positive benefits persisted for up to 12 months, and the majority of participants expressed satisfaction. SVF from each patient was stored in a liquid nitrogen freezer for future clinical treatments. Unique to this study of autologous cells is the shipment of lipoaspirate from the clinic to a central FDA-compliant manufacturing facility for cleanroom-controlled manufacturing. The cell product characterization data demonstrate that this method produces an equivalent product in terms of cell count and viability with the added benefit of further quality assurance testing, including sterility, endotoxin, and flow cytometry, before patient administration. Clinical Trial Registration Number: NCT04043819.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"168-176"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11036882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear Factor I A and Nuclear Factor I B Are Jointly Required for Mouse Postnatal Neural Stem Cell Self-Renewal.","authors":"Christine E Campbell, Karstin Webber, Jonathan E Bard, Lee D Chaves, Jason M Osinski, Richard M Gronostajski","doi":"10.1089/scd.2022.0204","DOIUrl":"10.1089/scd.2022.0204","url":null,"abstract":"<p><p>Mouse postnatal neural stem cells (pNSCs) can be expanded in vitro in the presence of epidermal growth factor and fibroblast growth factor 2 and upon removal of these factors cease proliferation and generate neurons, astrocytes, and oligodendrocytes. The genetic requirements for self-renewal and lineage-commitment of pNSCs are incompletely understood. In this study, we show that the transcription factors NFIA and NFIB, previously shown individually, to be essential for the normal commitment of pNSCs to the astrocytic lineage in vivo, are jointly required for normal self-renewal of pNSCs in vitro and in vivo. Using conditional knockout alleles of <i>Nfia</i> and <i>Nfib</i>, we show that the simultaneous loss of these two genes under self-renewal conditions in vitro reduces the expression of the proliferation markers PCNA and Ki67, eliminates clonogenicity of the cells, reduces the number of cells in S phase, and induces aberrant differentiation primarily into the neuroblast lineage. This phenotype requires the loss of both genes and is not seen upon loss of <i>Nfia</i> or <i>Nfib</i> alone, nor with combined loss of <i>Nfia</i> and <i>Nfix</i> or <i>Nfib</i> and <i>Nfix</i>. These data demonstrate a unique combined requirement for both <i>Nfia</i> and <i>Nfib</i> for pNSC self-renewal.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"153-167"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139748010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Seipin on Mouse Mesenchymal Stem Cell Osteo-Adipogenic Balance.","authors":"Zeying Li, Shan Jin, Tong Xu, Hongzhi Chen, Wenping Cai, Jin Du, Jin Qiu, Sihui Zhuang, Yan Qi, Wenyi Gu, Lijuan Pang","doi":"10.1089/scd.2023.0107","DOIUrl":"10.1089/scd.2023.0107","url":null,"abstract":"<p><p>Seipin deficiency is an important cause of type 2 Berardinelli-Seip congenital dyslipidemia (BSCL2). BSCL2 is a severe lipodystrophy syndrome with lack of adipose tissue, hepatic steatosis, insulin resistance, and normal or higher bone mineral density. Bone marrow mesenchymal stem cells (BMSCs) are believed to maintain bone and fat homeostasis by differentiating into osteoblasts and adipocytes. We aimed to explore the role of seipin in the osteogenic/adipogenic differentiation balance of BMSCs. Seipin loxP/loxP mice are used to explore metabolic disorders caused by <i>seipin</i> gene mutations. Compared with wild-type mice, subcutaneous fat deficiency and ectopic fat accumulation were higher in seipin knockout mice. Microcomputed tomography of the tibia revealed the increased bone content in seipin knockout mice. We generated seipin-deficient BMSCs in vitro and revealed that lipogenic genes are downregulated and osteogenic genes are upregulated in seipin-deficient BMSCs. In addition, peroxisome proliferator-activated receptor gamma (PPARγ) signaling is reduced in seipin-deficient BMSCs, while using the PPARγ activator increased the lipogenic differentiation and decreased osteogenic differentiation of seipin-deficient BMSCs. Our findings indicated that bone and lipid metabolism can be regulated by seipin through modulating the differentiation of mesenchymal stem cells. Thus, a new insight of seipin mutations in lipid metabolism disorders was revealed, providing a prospective strategy for MSC transplantation-based treatment of BSCL2.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"177-188"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}