Functional hit 1 (FH1)-based rapid and efficient generation of functional hepatocytes from human mesenchymal stem cells: a novel strategy for hepatic differentiation.
Functional hit 1 (FH1)-based rapid and efficient generation of functional hepatocytes from human mesenchymal stem cells: a novel strategy for hepatic differentiation.
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DOI：
10.21037/atm-21-2829
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发表时间：
2021-07
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Luo S;Ai Y;Xiao S;Wang B;Wang Y
由于肝脏是机体生理的中心，原代肝细胞被广泛应用于肝脏病理和生理研究，如肝脏药物筛选，生物人工肝支持系统和肝脏疾病的细胞治疗。然而，原代肝细胞的来源有限。我们描述了一种新型的非转基因方案，该方案有助于从人脐带来源的间充质干细胞（hUC-MSC）快速生成肝细胞样细胞，提供了功能性肝细胞的新来源。在这项研究中，我们使用hUC-MSCs和人诱导多能细胞（iPSCs）来源的间充质干细胞（iMSCs）来研究新的诱导策略。采用小分子化合物联合细胞因子体外诱导第3代骨髓间充质干细胞向肝细胞样细胞分化。FH 1是一种很有前途的小分子化合物，在肝细胞成熟阶段替代HGF诱导肝细胞样细胞分化。我们在体外10天内快速诱导hUC-MSC和人iMSC为肝细胞样细胞，并且细胞在形态上类似于来自基于肝细胞生长因子（HGF）的方法的肝细胞和原代肝细胞。它们表达成熟肝细胞特异性基因，实现糖原储存、白蛋白表达、尿素分泌、细胞色素P450活性、低密度脂蛋白（LDL）摄取和吲哚菁绿色（ICG）摄取等功能。我们成功地建立了一种不使用HGF的小分子方案来将MSC分化为肝细胞样细胞，这为肝脏疾病的体外研究提供了快速且具有成本效益的平台。
Because the liver is central to the physiology of the body, primary hepatocytes are widely used in liver pathology and physiological research, such as liver drug screening, bioartificial liver support system, and cell therapy for liver diseases. However, the source of primary hepatocytes is limited. We describe a novel non-transgenic protocol that facilitates the rapid generation of hepatocyte-like cells from human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), providing a new source of functional hepatocytes. In this study, we used hUC-MSCs and human induced pluripotent cells (iPSCs) derived mesenchymal stem cells (iMSCs) to investigate the new induction strategy. Passage 3 MSCs were induced into hepatocyte-like cells using small-molecule compounds combined with cell factors in vitro. Functional hit 1 (FH1), a promising small molecule compound was achieved to replace HGF in the hepatocyte maturation stage to induce the hepatocyte-like cells differentiation. We rapidly induced hUC-MSCs and human iMSCs into hepatocyte-like cells within 10 days in vitro, and the cells were morphologically similarly to both hepatocytes derived from the hepatocyte growth factor (HGF)-based method and the primary hepatocytes. They expressed mature hepatocyte special genes and achieved functions such as glycogen storage, albumin expression, urea secretion, cytochrome P450 activity, Low-density lipoprotein (LDL) uptake, and indocyanine green (ICG) uptake. We successfully established a small-molecule protocol without using HGF to differentiate MSCs into hepatocyte-like cells, which provides a rapid and cost-effective platform for in vitro studies of liver disease.
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从人类脂肪干细胞中快速生成功能性肝细胞样细胞
影响因子：
7.5
作者：
Fu Y;Deng J;Jiang Q;Wang Y;Zhang Y;Yao Y;Cheng F;Chen X;Xu F;Huang M;Yang Y;Zhang S;Yu D;Zhao RC;Wei Y;Deng H
通讯作者：
Deng H
影响因子：
4.3
作者：
Hu C;Li L
通讯作者：
Li L
影响因子：
0.7
作者：
Romanov, YA;Darevskava, AN;Buravkova, LB
通讯作者：
Buravkova, LB
DOI：
10.1242/dev.114215
发表时间：
2015-06-15
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Gordillo M;Evans T;Gouon-Evans V
通讯作者：
Gouon-Evans V
影响因子：
4.6
作者：
Engert, Silvia;Burtscher, Ingo;Lickert, Heiko
通讯作者：
Lickert, Heiko