Induction of the differentiation of porcine bone marrow mesenchymal stem cells into premature hepatocyte-like cells in an indirect coculture system with primary hepatocytes

被引:4
|
作者
Ullah, Imran [1 ,2 ]
Seo, Kangmin [1 ]
Wi, Hayeon [1 ]
Kim, Youngim [1 ]
Lee, Seunghoon [1 ]
Ock, Sun A. [1 ]
机构
[1] Rural Dev Adm, Natl Inst Anim Sci, Anim Biotechnol Div, Wanju Gun, South Korea
[2] Quaid I Azam Univ, Dept Biochem, Islamabad, Pakistan
关键词
Mesenchymal stem cells; bone marrow mesenchymal stem cells; hepatocyte-like cells; coculture; Transwell system; HEPATIC DIFFERENTIATION; LIVER-TRANSPLANTATION; GROWTH-FACTOR; ONCOSTATIN M; CULTURE;
D O I
10.1080/19768354.2020.1823473
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Liver transplantation is currently the only option for patients with end-stage liver disease. Thus, other alternate therapeutic strategies are needed. Bone marrow mesenchymal stem cells (BM-MSCs) are nonhematopoietic cells present in the bone marrow stroma that serve as precursors cells for various other cells. In this study, we evaluated the differentiation of porcine BM-MSCs into hepatocyte-like cells using three types of culture systems: hepatic induction medium (HIM), HIM/primary hepatocyte culture supernatant (HCS; 1:1 ratio), and a hepatocyte coculture system (HCCS; primary hepatocytes in the upper chamber, and BM-MSCs in the lower chamber). Primary hepatocytes were isolated from anesthetized healthy 1-month-old pigs by enzymatic digestion. Hepatic-specific marker expression (albumin [ALB], transferrin [TF], alpha-fetoprotein [AFP]), glycogen storage, low-density lipoprotein, and indocyanine green uptake were evaluated. Upregulation of hepatic-specific markers (ALB,TF, andAFP) was observed by real-time polymerase chain reaction in the HCCS group. Periodic acid-Schiff staining revealed enhanced glycogen storage in hepatocyte-like cells from the HCCS group compared with that from the HIM/HCS group. Furthermore, hepatocyte like-cells in the HCCS group showed improved LDL and ICG uptake than those in the other groups. Overall, our current study revealed that indirect coculture of primary hepatocytes and BM-MSCs enhanced the differentiation efficacy of BM-MSCs into hepatocyte-like cells by unknown useful soluble factors, including paracrine factors.
引用
收藏
页码:289 / 298
页数:10
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