Establishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy

Globally, about two million people die from liver diseases every year. Liver transplantation is the only reliable therapy for severe end-stage liver disease, however, the shortage of organ donors is a huge limitation. Human hepatocytes derived liver progenitor-like cells (HepLPCs) have been reported...

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Autores principales:	Wen-Ming Liu, Xu Zhou, Cai-Yang Chen, Dong-Dong Lv, Wei-Jian Huang, Yuan Peng, Hong-Ping Wu, Yi Chen, Dan Tang, Li-Na Guo, Xiu-Li Wang, Hong-Dan Zhang, Xiao-Hua Liu, Li-Qun Yang, Wei-Feng Yu, He-Xin Yan
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	human hepatocytes derived liver progenitor-like cells spheroids transplantation acute liver failure intraperitoneal transplantation cell therapy alginate microencapsulation Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/dd246c3447cd4c2f890b1f3731f31c8f
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spelling	oai:doaj.org-article:dd246c3447cd4c2f890b1f3731f31c8f2021-11-08T06:22:54ZEstablishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy2296-418510.3389/fbioe.2021.738081https://doaj.org/article/dd246c3447cd4c2f890b1f3731f31c8f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.738081/fullhttps://doaj.org/toc/2296-4185Globally, about two million people die from liver diseases every year. Liver transplantation is the only reliable therapy for severe end-stage liver disease, however, the shortage of organ donors is a huge limitation. Human hepatocytes derived liver progenitor-like cells (HepLPCs) have been reported as a novel source of liver cells for development of in vitro models, cell therapies, and tissue-engineering applications, but their functionality as transplantation donors is unclear. Here, a 3-dimensional (3D) co-culture system using HepLPCs and human umbilical vein endothelial cells (HUVECs) was developed. These HepLPC spheroids mimicked the cellular interactions and architecture of mature hepatocytes, as confirmed through ultrastructure morphology, gene expression profile and functional assays. HepLPCs encapsulated in alginate beads are able to mitigate liver injury in mice treated with carbon tetrachloride (CCL4), while alginate coating protects the cells from immune attack. We confirmed these phenomena due to HUVECs producing glial cell line-derived neurotrophic factor (GDNF) to promote HepLPCs maturation and enhance HepLPCs tight junction through MET phosphorylation. Our results display the efficacy and safety of the alginate microencapsulated spheroids in animal model with acute liver injury (ALF), which may suggest a new strategy for cell therapy.Wen-Ming LiuWen-Ming LiuXu ZhouXu ZhouCai-Yang ChenCai-Yang ChenDong-Dong LvWei-Jian HuangWei-Jian HuangYuan PengHong-Ping WuYi ChenYi ChenDan TangDan TangLi-Na GuoXiu-Li WangHong-Dan ZhangXiao-Hua LiuXiao-Hua LiuLi-Qun YangLi-Qun YangWei-Feng YuWei-Feng YuHe-Xin YanHe-Xin YanHe-Xin YanHe-Xin YanFrontiers Media S.A.articlehuman hepatocytes derived liver progenitor-like cellsspheroids transplantationacute liver failureintraperitoneal transplantationcell therapyalginate microencapsulationBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human hepatocytes derived liver progenitor-like cells spheroids transplantation acute liver failure intraperitoneal transplantation cell therapy alginate microencapsulation Biotechnology TP248.13-248.65
spellingShingle	human hepatocytes derived liver progenitor-like cells spheroids transplantation acute liver failure intraperitoneal transplantation cell therapy alginate microencapsulation Biotechnology TP248.13-248.65 Wen-Ming Liu Wen-Ming Liu Xu Zhou Xu Zhou Cai-Yang Chen Cai-Yang Chen Dong-Dong Lv Wei-Jian Huang Wei-Jian Huang Yuan Peng Hong-Ping Wu Yi Chen Yi Chen Dan Tang Dan Tang Li-Na Guo Xiu-Li Wang Hong-Dan Zhang Xiao-Hua Liu Xiao-Hua Liu Li-Qun Yang Li-Qun Yang Wei-Feng Yu Wei-Feng Yu He-Xin Yan He-Xin Yan He-Xin Yan He-Xin Yan Establishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy
description	Globally, about two million people die from liver diseases every year. Liver transplantation is the only reliable therapy for severe end-stage liver disease, however, the shortage of organ donors is a huge limitation. Human hepatocytes derived liver progenitor-like cells (HepLPCs) have been reported as a novel source of liver cells for development of in vitro models, cell therapies, and tissue-engineering applications, but their functionality as transplantation donors is unclear. Here, a 3-dimensional (3D) co-culture system using HepLPCs and human umbilical vein endothelial cells (HUVECs) was developed. These HepLPC spheroids mimicked the cellular interactions and architecture of mature hepatocytes, as confirmed through ultrastructure morphology, gene expression profile and functional assays. HepLPCs encapsulated in alginate beads are able to mitigate liver injury in mice treated with carbon tetrachloride (CCL4), while alginate coating protects the cells from immune attack. We confirmed these phenomena due to HUVECs producing glial cell line-derived neurotrophic factor (GDNF) to promote HepLPCs maturation and enhance HepLPCs tight junction through MET phosphorylation. Our results display the efficacy and safety of the alginate microencapsulated spheroids in animal model with acute liver injury (ALF), which may suggest a new strategy for cell therapy.
format	article
author	Wen-Ming Liu Wen-Ming Liu Xu Zhou Xu Zhou Cai-Yang Chen Cai-Yang Chen Dong-Dong Lv Wei-Jian Huang Wei-Jian Huang Yuan Peng Hong-Ping Wu Yi Chen Yi Chen Dan Tang Dan Tang Li-Na Guo Xiu-Li Wang Hong-Dan Zhang Xiao-Hua Liu Xiao-Hua Liu Li-Qun Yang Li-Qun Yang Wei-Feng Yu Wei-Feng Yu He-Xin Yan He-Xin Yan He-Xin Yan He-Xin Yan
author_facet	Wen-Ming Liu Wen-Ming Liu Xu Zhou Xu Zhou Cai-Yang Chen Cai-Yang Chen Dong-Dong Lv Wei-Jian Huang Wei-Jian Huang Yuan Peng Hong-Ping Wu Yi Chen Yi Chen Dan Tang Dan Tang Li-Na Guo Xiu-Li Wang Hong-Dan Zhang Xiao-Hua Liu Xiao-Hua Liu Li-Qun Yang Li-Qun Yang Wei-Feng Yu Wei-Feng Yu He-Xin Yan He-Xin Yan He-Xin Yan He-Xin Yan
author_sort	Wen-Ming Liu
title	Establishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy
title_short	Establishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy
title_full	Establishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy
title_fullStr	Establishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy
title_full_unstemmed	Establishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy
title_sort	establishment of functional liver spheroids from human hepatocyte-derived liver progenitor-like cells for cell therapy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/dd246c3447cd4c2f890b1f3731f31c8f
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Establishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy

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