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

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 fr...

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Autores principales: Lee, Jooyoung, Choi, Jiwan, Kang, Seoon, Kim, Jiye, Lee, Ryunjin, So, Seongjun, Yoon, Young-In, Kirchner, Varvara A., Song, Gi-Won, Hwang, Shin, Lee, Sung-Gyu, Kang, Eunju, Tak, Eunyoung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348751/
https://www.ncbi.nlm.nih.gov/pubmed/32580448
http://dx.doi.org/10.3390/cells9061521
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author Lee, Jooyoung
Choi, Jiwan
Kang, Seoon
Kim, Jiye
Lee, Ryunjin
So, Seongjun
Yoon, Young-In
Kirchner, Varvara A.
Song, Gi-Won
Hwang, Shin
Lee, Sung-Gyu
Kang, Eunju
Tak, Eunyoung
author_facet Lee, Jooyoung
Choi, Jiwan
Kang, Seoon
Kim, Jiye
Lee, Ryunjin
So, Seongjun
Yoon, Young-In
Kirchner, Varvara A.
Song, Gi-Won
Hwang, Shin
Lee, Sung-Gyu
Kang, Eunju
Tak, Eunyoung
author_sort Lee, Jooyoung
collection PubMed
description 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.
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spelling pubmed-73487512020-07-20 Hepatogenic Potential and Liver Regeneration Effect of Human Liver-derived Mesenchymal-Like Stem Cells Lee, Jooyoung Choi, Jiwan Kang, Seoon Kim, Jiye Lee, Ryunjin So, Seongjun Yoon, Young-In Kirchner, Varvara A. Song, Gi-Won Hwang, Shin Lee, Sung-Gyu Kang, Eunju Tak, Eunyoung Cells Article 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. MDPI 2020-06-22 /pmc/articles/PMC7348751/ /pubmed/32580448 http://dx.doi.org/10.3390/cells9061521 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Jooyoung
Choi, Jiwan
Kang, Seoon
Kim, Jiye
Lee, Ryunjin
So, Seongjun
Yoon, Young-In
Kirchner, Varvara A.
Song, Gi-Won
Hwang, Shin
Lee, Sung-Gyu
Kang, Eunju
Tak, Eunyoung
Hepatogenic Potential and Liver Regeneration Effect of Human Liver-derived Mesenchymal-Like Stem Cells
title Hepatogenic Potential and Liver Regeneration Effect of Human Liver-derived Mesenchymal-Like Stem Cells
title_full Hepatogenic Potential and Liver Regeneration Effect of Human Liver-derived Mesenchymal-Like Stem Cells
title_fullStr Hepatogenic Potential and Liver Regeneration Effect of Human Liver-derived Mesenchymal-Like Stem Cells
title_full_unstemmed Hepatogenic Potential and Liver Regeneration Effect of Human Liver-derived Mesenchymal-Like Stem Cells
title_short Hepatogenic Potential and Liver Regeneration Effect of Human Liver-derived Mesenchymal-Like Stem Cells
title_sort hepatogenic potential and liver regeneration effect of human liver-derived mesenchymal-like stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348751/
https://www.ncbi.nlm.nih.gov/pubmed/32580448
http://dx.doi.org/10.3390/cells9061521
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