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Therapeutic Potential of Human-induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells in Mice with Lethal Fulminant Hepatic Failure.
Cell Transplant. 2013 Feb 5. [Epub ahead of print] doi:
Moslem M, Valojerdi MR, Pournasr B, Muhammadnejad A, Baharvand H
Abstract:
Large-scale production and noninvasive methods for harvesting mesenchymal stem cells (MSCs), particularly in elderly individuals, has prompted researchers to find new patientspecific sources for MSCs in regenerative medicine. This study aims to produce mesenchymal stem cells (MSCs) from human induced pluripotent stem cells (hiPSCs) and to evaluate their therapeutic effects in a CCl₄-induced mouse model of fulminant hepatic failure (FHF). hiPSCMSCs have shown MSCs morphology, antigen profile and differentiation capabilities, and improved hepatic function in our model. hiPSC-MSCs transplanted animals provide significant benefit in terms of survival, serum LDH, total bilirubin, and lipid peroxidation. hiPSC-MSCs therapy resulted in a one-third reduction of histologic activity index and a threefold increase in the number of proliferating hepatocytes. This was accompanied by a significant decrease in the expression levels of collagen type I, Mmp13, Mmp2, and Mmp9 genes and increase in Timp1 and Timp2 genes in transplanted groups. hiPSC-MSCs secreted hepatocyte growth factor (HGF) in vitro and also expressed HGF in evaluated liver sections. Similar results were observed with human bone marrow (hBM)-derived MSCs. In conclusion, our results have demonstrated that hiPSC-MSCs might be valuable appropriate alternatives for hBM-MSCs in FHF liver repair and support liver function by cell therapy with a large-scale production capacity, patient-specific nature and no invasive MSC harvesting.