Clonal Mesenchymal Stem Cells Derived From Human Bone Marrow Can Differentiate Into Hepatocyte-Like Cells in Injured Livers of SCID Mice
Clonal Mesenchymal Stem Cells Derived From Human Bone Marrow Can Differentiate Into Hepatocyte-Like Cells in Injured Livers of SCID Mice
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DOI：
10.1002/jcb.22306
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发表时间：
2009-10-15
影响因子：
4
通讯作者：
Hu, Yi-Ping
中科院分区：
文献类型：
--
作者：
Tao, Xin-Rong;Li, Wen-Lin;Hu, Yi-Ping
越来越多的证据表明，人间充质干细胞（hMSCs）是一种有价值的、可移植的肝细胞来源。这些研究中使用的大多数hMSCs制剂可能是异质细胞群，通过粘附在塑料表面或密度梯度离心分离。因此，其他未知的微量细胞群的参与不能严格地打折扣。本文报道了从人骨髓原代培养中分离并建立了克隆的人骨髓间充质干细胞系（chMSC），并证实了其肝脏分化能力。chMSCs表达间充质细胞标记物，但不表达造血干细胞标记物。在体外，chMSCs可以分化为间充质细胞或表现出肝细胞样表型的细胞。将egfp标记的chMSCs经脾内移植到四氯化碳损伤的SCID小鼠肝脏中，移植到宿主肝脏实质中，呈现典型的肝细胞形态，形成三维结构，并分化为表达人白蛋白和α -1-抗胰蛋白酶的肝细胞样细胞。共聚焦显微镜下，移植肝细胞和宿主肝细胞间可见超细的细胞间纳米管结构。我们假设这些结构可能通过在原生肝细胞和移植细胞之间交换细胞质成分来协助chMSCs的表型转化。因此，可以在培养中扩增的克隆纯hMSCs群体可能具有替代肝损伤中受损细胞的细胞来源的潜力。j .细胞。中国生物医学工程学报，2009,31(2):444 - 444。(C) 2009 Wiley-Liss, Inc。
There is increasing evidence that human mesenchymal stem cells (hMSCs) can be a valuable, transplantable source of hepatocytes. Most of the hMSCs preparations used in these studies were likely heterogeneous cell populations, isolated by adherence to plastic surfaces or by density gradient centrifugation. Therefore, the participation of other unknown trace cell populations cannot be rigorously discounted. Here we report the isolation and establishment of a cloned human MSC line (chMSC) from human bone marrow primary culture, through which we confirmed the hepatic differentiation capability of authentic hMSCs. chMSCs expressed markers of mesenchymal cells, but not markers of hematopoietic stem cells. In vitro, chMSCs can differentiate into either mesenchymal cells or cells exhibiting hepatocyte-like phenotypes. When transplanted intrasplentically into carbon tetrachloride-injured livers of SCID mice, EGFP-tagged chMSCs engrafted into the host liver parenchyma, exhibited typical hepatocyte morphology, form a three-dimensional architecture, and differentiate into hepatocyte-like cells expressing human albumin and alpha-1-anti-trypsin. By confocal microscopy, ultrafine intercellular nanotubular structures were visible between adjacent transplanted and host hepatocytes. We postulate that these structures may assist in the phenotype conversion of chMSCs, possibly by exchange of cytoplasmic components between native hepatocytes and transplanted cells. Thus, a clonal pure population of hMSCs, which can be expanded in culture, may have potential as a cellular source for substitution damaged cells in hepatic injury. J. Cell. Biochem. 108: 693704, 2009. (C) 2009 Wiley-Liss, Inc.