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

Jooyoung Lee, Jiwan Choi, Seoon Kang, Jiye Kim, Ryunjin Lee, Seongjun So, Young In Yoon, Varvara A. Kirchner, Gi Won Song, Shin Hwang, Sung Gyu Lee, Eunju Kang, Eunyoung Tak

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalCells
Volume9
Issue number6
DOIs
StatePublished - Jun 22 2020

Keywords

  • acute liver injury
  • cell transplantation
  • hepatic differentiation
  • hepatocyte-like cell
  • human liver-derived stem cell
  • regenerative medicine

PubMed: MeSH publication types

  • Journal Article

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