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Liver epithelioid progenitor cells derived from fetal Luxi bovine alleviate liver fibrosis.

ABSTRACT: Liver epithelioid progenitor cells (LEPCs) have important roles in liver therapy because of their hepatic differentiation potency in vitro and in vivo. Despite many researches on humans, mice, and rats, equivalent progenitor cells derived from bovine are relatively rare. The purpose of our current study is to characterize bovine LEPCs, and research on the cure potency of this heteroplastic progenitor cells on mice liver fibrosis. We have used collagenase IV digesting and differential adhesion method to isolate slabstone shape, EpCAM, LGR5, NCAM1 and SOX9 positive progenitor cells from fetal Luxi bovine liver. When cultured in hepatic differentiation media containing 20 ng/ml Oncostatin M, LEPCs can differentiate into hepatocytes in vitro. After 4 weeks of intravenous tail vein injection into CCl₄-injured mouse liver, LEPCs engrafted into liver parenchyma, differentiated into ALB positive hepatocytes, and could alleviate liver fibrosis through down regulating fibrosis genes-Tgfb1 and ?-SMA as well as decreasing expression of collagen gene Col1a1, Col3a1, and Col4a1, and regain liver function by recovering ALT and AST. Our findings provided a useful tool for studying liver development in vitro, new cell resource for heterograft on mouse liver diseases, and a new platform for researches on immune rejection of heterogeneous cell transplantation.

SUBMITTER: Wang K

PROVIDER: S-EPMC5809641 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Liver epithelioid progenitor cells derived from fetal Luxi bovine alleviate liver fibrosis.

Wang Kunfu K Liu Hao H Yang Jinjuan J Ma Caiyun C Zhang Zebiao Z Zheng Dong D Guan Weijun W

Cytotechnology 20170617 1

Liver epithelioid progenitor cells (LEPCs) have important roles in liver therapy because of their hepatic differentiation potency in vitro and in vivo. Despite many researches on humans, mice, and rats, equivalent progenitor cells derived from bovine are relatively rare. The purpose of our current study is to characterize bovine LEPCs, and research on the cure potency of this heteroplastic progenitor cells on mice liver fibrosis. We have used collagenase IV digesting and differential adhesion me ...[more]

PMID: 28625011

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Project description:INTRODUCTION: With the shortage of donor organs for islet transplantation, insulin-producing cells have been generated from different types of stem cell. Human fetal pancreatic stem cells have a better self-renewal capacity than adult stem cells and can readily differentiate into pancreatic endocrine cells, making them a potential source for islets in diabetes treatment. In the present study, the functions of pancreatic islets derived from human fetal pancreatic progenitor cells were evaluated in vitro and in vivo. METHODS: Human pancreatic progenitor cells isolated from the fetal pancreas were expanded and differentiated into islet endocrine cells in culture. Markers for endocrine and exocrine functions as well as those for alpha and beta cells were analyzed by immunofluorescent staining and enzyme-linked immunosorbent assay (ELISA). To evaluate the functions of these islets in vivo, the islet-like structures were transplanted into renal capsules of diabetic nude mice. Immunohistochemical staining for human C-peptide and human mitochondrion antigen was applied to confirm the human origin and the survival of grafted islets. RESULTS: Human fetal pancreatic progenitor cells were able to expand in medium containing basic fibroblast growth factor (bFGF) and leukemia inhibitor factor (LIF), and to differentiate into pancreatic endocrine cells with high efficiency upon the actions of glucagon-like peptide-1 and activin-A. The differentiated cells expressed insulin, glucagon, glucose transporter-1 (GLUT1), GLUT2 and voltage-dependent calcium channel (VDCC), and were able to aggregate into islet-like structures containing alpha and beta cells upon suspension. These structures expressed and released a higher level of insulin than adhesion cultured cells, and helped to maintain normoglycemia in diabetic nude mice after transplantation. CONCLUSIONS: Human fetal pancreatic progenitor cells have good capacity for generating insulin producing cells and provide a promising potential source for diabetes treatment.

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Liver epithelioid progenitor cells derived from fetal Luxi bovine alleviate liver fibrosis.

Publications

Liver epithelioid progenitor cells derived from fetal Luxi bovine alleviate liver fibrosis.

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