Project description:Gunn rats bear a mutation within the uridine diphosphate glucuronosyltransferase-1A1 (Ugt1A1) gene resulting in high serum bilirubin levels as seen in Crigler-Najjar syndrome. In the present study, the Gunn rat was used as an animal model for heritable liver dysfunction. Human pluripotent stem cell-derived mesenchymal stem cells (iMSCs) were transplanted into Gunn rats after partial hepatectomy. The iMSCs engrafted and survived in the liver for up to 2 months without the need for immunosuppression. The transplanted iMSCs differentiated into functional hepatocytes and partially suppressed hyperbilirubinemia. Furthermore, human Albumin as well as the human immunomodulatory factors, RANTES and SERPINE1, were detected in the rat serum upon iMSC transplantation. The differentiation of iMSCs into hepatocytes was confirmed by qPCR and/or immunohistochemistry, detecting expression of human hepatocyte nuclear factor 4α, UGT1A1, cytokeratin 18, α-fetoprotein and Albumin. These findings indicate transplanted iMSCs differentiated into hepatocytes and thus contributed to tissue repair in an injury model of hepatocyte-based liver regeneration.
Project description:Hematopoietic stem cells (HSCs) can regenerate the entire hematopoietic system in vivo, providing the most relevant criteria to measure candidate HSCs derived from human embryonic stem cell (hESC) or induced pluripotent stem cell (hiPSC) sources. Here, we show that unlike primitive hematopoietic cells derived from hESCs, phenotypically identical cells derived from hiPSC are more permissive to graft the bone marrow of xenotransplantation recipients. Despite establishment of bone marrow graft, hiPSC-derived cells fail to demonstrate hematopoietic differentiation in vivo. However, once removed from recipient bone marrow, hiPSC-derived grafts were capable of in vitro multilineage hematopoietic differentiation, indicating that xenograft imparts a restriction to in vivo hematopoietic progression. This failure to regenerate multilineage hematopoiesis in vivo was attributed to the inability to downregulate key microRNAs involved in hematopoiesis. Based on these analyses, our study indicates that hiPSCs provide a beneficial source of pluripotent stem cell-derived hematopoietic cells for transplantation compared with hESCs. Since use of the human-mouse xenograft models prevents detection of putative hiPSC-derived HSCs, we suggest that new preclinical models should be explored to fully evaluate cells generated from hiPSC sources. Human pluripotent stem cell-derived hematopoietic cells were isolated and qPCR-based microRNA profiling was performed.
Project description:Global gene expression data of human embryonic stem cell-, human induced pluripotent stem cell- and bone marrow-derived mesenchymal progenitor cells before and after culture onto osteoinductive scaffolds in perfusion bioreactors. The hypothesis tested in the present study was that perfusion culture in bioreactors influenced the expression levels of several genes involved in proliferation and osteogenic differentiation. Results provide important information of the response of human embryonic stem cell-, human induced pluripotent stem cell- and bone marrow-derived mesenchymal progenitor cell to osteogenic stimulation under perfusion cultures, such as genes involved in cell proliferation and division as well as osteogenic differentiation and bone development. Total RNA obtained from human embryonic stem cell-, human induced pluripotent stem cell- and bone marrow-derived mesenchymal progenitor cells before and after culture under osteogenic conditions in perfusion bioreactors for 5 weeks.
Project description:We analyzed gene expression profiles of self-organizing, multi-cellular, 3D liver organoids derived by co-culture of induced Pluripotent Stem Cell and stromal progenitors. We report the RNA-seq results of liver organoid at day0, day2, day4, day6 of co-culture. We also report RNA-seq results of constituent of the liver organoid, which are human iPSC at hepatic specification stage, human Mesenchymal stem cells derived from bone marrow, human umbilical vein endothelial cell. As controls, we also report RNS-seq results of un-differentiated human iPSC, human iPSC at definitive endoderm stage, human liver tissue, and primary cultured human hepatocytes isolated from unused donor livers.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Increasing studies suggested the treatment potential of mesenchymal stem cells in variety diseases. Evidence showed that MSCs could promote injured tissue repair and improve disease mortality. These indicated that MSC transplantation may be an ideal candidate for cholestasis treatment.We found that MenSC transplantation could significantly improve the symptoms and pathological changes of DDC-induced cholestasis liver injury in mice.
Project description:Comparison of whole genome gene expression profiles of human testis derived ES-like cells with pluripotent stem cells (human embryonic stem cell lines), adult human bone marrow derived mesenchymal stem cells and human dermal fibroblasts.