Journal
CELL TRANSPLANTATION
Volume 22, Issue 10, Pages 1785-1799Publisher
COGNIZANT COMMUNICATION CORP
DOI: 10.3727/096368912X662462
Keywords
Human induced pluripotent stem cells (hiPSCs); Mesenchymal stem cells (MSCs); Fulminant hepatic failure (FHF)
Funding
- Royan Institute and Iranian Council of Stem Cell Research and Technology
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Large-scale production and noninvasive methods for harvesting mesenchymal stem cells (MSCs), particularly in elderly individuals, has prompted researchers to find new patient-specific sources for MSCs in regenerative medicine. This study aims to produce 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). hiPSC-MSCs have shown MSC morphology, antigen profile and differentiation capabilities, and improved hepatic function in our model. hiPSC-MSC-transplanted animals provide significant benefit in terms of survival, serum LDH, total bilirubin, and lipid peroxidation. hiPSC-MSC 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, MmpI3, Mmp2, and Mmp9 genes and increase in Timpl 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.
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