Hepatogenic Potential and Liver Regeneration Effect of Human Liver-derived Mesenchymal-Like Stem Cells

Cells

Seongjun So¹  Sung-Gyu Lee²  Gi-Won Song³  Eunyoung Tak³  Ryunjin Lee⁴  Jooyoung Lee⁵  Jiye Kim⁵  Seoon Kang⁵  Young-In Yoon⁵  Jiwan Choi⁵  Eunju Kang⁶  VarvaraA. Kirchner⁶  Shin Hwang⁷ 

[1] and Asan-Minnesota Institute for Innovating Transplantation (AMIT), Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea;and Asan-Minnesota Institute for Innovating Transplantation (AMIT), University of Minnesota, Minneapolis, MN 55455, USA;and Asan-Minnesota Institute for Innovating Transplantation (AMIT), University of Ulsan College of Medicine, Seoul 05505, Korea;Biomedical Research Center, Asan Institute for Life Sciences;Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology (AMIST), Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea;Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery;Division of Transplantation, Department of Surgery;

关键词: human liver-derived stem cell;    hepatic differentiation;    hepatocyte-like cell;    acute liver injury;    regenerative medicine;    cell transplantation;   

DOI  :  10.3390/cells9061521

来源: DOAJ

【 摘 要 】

Human liver-derived stem cells (hLD-SCs) have been proposed as a possible resource for stem cell therapy in patients with irreversible liver diseases. However, it is not known whether liver resident hLD-SCs can differentiate toward a hepatic fate better than mesenchymal stem cells (MSCs) obtained from other origins. In this study, we compared the differentiation ability and regeneration potency of hLD-SCs with those of human umbilical cord matrix-derived stem cells (hUC-MSCs) by inducing hepatic differentiation. Undifferentiated hLD-SCs expressed relatively high levels of endoderm-related markers (GATA4 and FOXA1). During directed hepatic differentiation supported by two small molecules (Fasudil and 5-azacytidine), hLD-SCs presented more advanced mitochondrial respiration compared to hUC-MSCs. Moreover, hLD-SCs featured higher numbers of hepatic progenitor cell markers on day 14 of differentiation (CPM and CD133) and matured into hepatocyte-like cells by day 7 through 21 with increased hepatocyte markers (ALB, HNF4A, and AFP). During in vivo cell transplantation, hLD-SCs migrated into the liver of ischemia-reperfusion injury-induced mice within 2 h and relieved liver injury. In the thioacetamide (TAA)-induced liver injury mouse model, transplanted hLD-SCs trafficked into the liver and spontaneously matured into hepatocyte-like cells within 14 days. These results collectively suggest that hLD-SCs hold greater hepatogenic potential, and hepatic differentiation-induced hLD-SCs may be a promising source of stem cells for liver regeneration.

【 授权许可】

Unknown