naa a22 4500 51073930X CHVBK 20180411083022.0 cr unu---uuuuu 180411e20130801xx s 000 0 eng 10.1007/s12015-011-9330-y doi (NATIONALLICENCE)springer-10.1007/s12015-011-9330-y Differentiation and Transplantation of Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells [Elektronische Daten] [Samira Asgari, Mohsen Moslem, Kamran Bagheri-Lankarani, Behshad Pournasr, Maryam Miryounesi, Hossein Baharvand] The generation of human induced pluripotent stem cells (hiPSCs) with a high differentiation potential provided a new source for hepatocyte generation not only for drug discovery and in vitro disease models, but also for cell replacement therapy. However, the reported hiPSC-derived hepatocyte-like cells (HLCs) were not well characterized and their transplantation, as the most promising clue of cell function was not reported. Here, we performed a growth factor-mediated differentiation of functional HLCs from hiPSCs and evaluated their potential for recovery of a carbon tetrachloride (CCl4)-injured mouse liver following transplantation. The hiPSC-derived hepatic lineage cells expressed hepatocyte-specific markers, showed glycogen and lipid storage activity, secretion of albumin (ALB), alpha-fetoprotein (AFP), urea, and CYP450 metabolic activity in addition to low-density lipoprotein (LDL) and indocyanin green (ICG) uptake. Similar results were observed with human embryonic stem cell (hESC)-derived HLCs. The transplantation of hiPSC-HLCs into a CCl4-injured liver showed incorporation of the hiPSC-HLCs into the mouse liver which resulted in a significant enhancement in total serum ALB after 1week. A reduction of total serum LDH and bilirubin was seen when compared with the control and sham groups 1 and 5weeks post-transplantation. Additionally, we detected human serum ALB and ALB-positive transplanted cells in both the host serum and livers, respectively, which showed functional integration of transplanted cells within the mouse livers. Therefore, our results have opened up a proof of concept that functional HLCs can be generated from hiPSCs, thus improving the general condition of a CCl4-injured mouse liver after their transplantation. These results may bring new insights in the clinical applications of hiPSCs once safety issues are overcome. Springer Science+Business Media, LLC, 2011 Human induced pluripotent stem cells nationallicence Human embryonic stem cells nationallicence Hepatocytes nationallicence Transplantation nationallicence Asgari Samira Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran aut Moslem Mohsen Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran aut Bagheri-Lankarani Kamran Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran aut Pournasr Behshad Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran aut Miryounesi Maryam Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran aut Baharvand Hossein Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran aut Stem Cell Reviews and Reports Springer US; http://www.springer-ny.com 9/4(2013-08-01), 493-504 1550-8943 9:4<493 2013 9 12015 https://doi.org/10.1007/s12015-011-9330-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12015-011-9330-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Asgari Samira Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran aut NATIONALLICENCE 700 1- Moslem Mohsen Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran aut NATIONALLICENCE 700 1- Bagheri-Lankarani Kamran Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran aut NATIONALLICENCE 700 1- Pournasr Behshad Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran aut NATIONALLICENCE 700 1- Miryounesi Maryam Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran aut NATIONALLICENCE 700 1- Baharvand Hossein Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran aut NATIONALLICENCE 773 0- Stem Cell Reviews and Reports Springer US; http://www.springer-ny.com 9/4(2013-08-01), 493-504 1550-8943 9:4<493 2013 9 12015 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer