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Cell Physiol Biochem. 2019;52(4):935-950. doi: 10.33594/000000065.

Human Adipose Derived Stem Cells Exhibit Enhanced Liver Regeneration in Acute Liver Injury by Controlled Releasing Hepatocyte Growth Factor.

Author information

1
Department of Internal Medicine, Catholic Kwandong University College of Medicine, International St. Mary's Hospital, Incheon, South Korea.
2
Department of Medicine, College of Medicine, Catholic Kwandong University, Gangneung, South Korea.
3
Department of Dental Hygiene, Masan University, Masan, South Korea.
4
Department of Medicine, College of Medicine, Catholic Kwandong University, Gangneung, South Korea, swkim@cku.ac.kr.

Abstract

BACKGROUND/AIMS:

Although mesenchymal stem cells (MSCs) provide effective therapy for liver fibrosis, there are conflicting data regarding their marginal therapeutic effects. This study aimed to enhance the potential of hepatocyte regeneration in human adipose mesenchymal stem cells (ASCs) and investigate whether they have robust therapeutic efficacy in experimental liver fibrosis.

METHODS:

ASCs were cultured with four cytokines (ASC-C), the expression of hepatogenic factors was detected by microarray, and the effects of conditioned medium (CM) from ASC-C on the activation of hepatic stellate cells were analyzed. The therapeutic effects and mechanism of liver fibrosis induced by thioacetamide (TAA) were determined after cell transplantation.

RESULTS:

ASC-C exhibited high levels of hepatogenic (HGF, G-CSF), anti-apoptotic (IGFBP-2), and chemokine (IL-8) genes and increased expression of hepatocyte specific proteins. ASC-C CM inhibited the activation of hepatic stellate cells in vitro, and injection of ASC-C significantly delayed TAA-induced liver fibrosis and improved liver function and regeneration in vivo. In addition, human albumin-expressing ASC-C were observed in the livers of recipient animals. High levels of expression of HGF and its downstream signaling molecules, including p-38, were detected in the ASC-C-injected livers. Transplantation of ASC-C exerts anti-fibrotic effects and accelerates liver regeneration.

CONCLUSION:

Thus, ASC-C may be a novel candidate for the enhanced treatment of liver cirrhosis in clinical settings.

KEYWORDS:

Growth factor; Liver cirrhosis; Mesenchymal stem cells; Regeneration

PMID:
30964610
DOI:
10.33594/000000065
[Indexed for MEDLINE]
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