Farzaneh Zahra, Pakzad Mohammad, Vosough Massoud, Pournasr Behshad, Baharvand Hossein
Department of Stem Cells and Developmental Biology at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, PO Box 19395-4644, Tehran, Iran.
Histochem Cell Biol. 2014 Aug;142(2):217-26. doi: 10.1007/s00418-014-1183-4. Epub 2014 Jan 30.
Human embryonic stem cells (hESCs) provide a new source for hepatocyte production in translational medicine and cell replacement therapy. The reported hESC-derived hepatocyte-like cells (HLCs) were commonly generated on Matrigel, a mouse cell line-derived extracellular matrix (ECM). Here, we performed the hepatic lineage differentiation of hESCs following a stepwise application of growth factors on a newly developed serum- and xeno-free, simple and cost-benefit ECM, designated "RoGel," which generated from a modified conditioned medium of human fibroblasts. In comparison with Matrigel, the differentiated HLCs on both ECMs expressed similar levels of hepatocyte-specific genes, secreted α-fetoprotein, and metabolized ammonia, showed glycogen storage activity as well as low-density lipoprotein and indocyanine green uptake. The transplantation of hESC-HLCs into the carbon tetrachloride-injured liver demonstrated incorporation of the cells into the host mouse liver and the expression of albumin. The results suggest that the xeno-free and cost-benefit matrix may be applicable in bioartificial livers and also may facilitating a clinical application of human pluripotent stem cell-derived hepatocytes in the future.
人类胚胎干细胞（hESCs）为转化医学和细胞替代疗法中的肝细胞生成提供了新来源。报道的源自hESCs的肝样细胞（HLCs）通常在基质胶（一种源自小鼠细胞系的细胞外基质（ECM））上生成。在此，我们在一种新开发的无血清、无异种成分、简单且具有成本效益的ECM（命名为“RoGel”，其由人成纤维细胞的改良条件培养基生成）上逐步应用生长因子，对hESCs进行肝系分化。与基质胶相比，在这两种ECM上分化的HLCs表达相似水平的肝细胞特异性基因，分泌甲胎蛋白并代谢氨，表现出糖原储存活性以及低密度脂蛋白和吲哚菁绿摄取能力。将hESC-HLCs移植到四氯化碳损伤的肝脏中，证明这些细胞整合到宿主小鼠肝脏中并表达白蛋白。结果表明，这种无异种成分且具有成本效益的基质可能适用于生物人工肝，并且在未来也可能促进人多能干细胞衍生的肝细胞的临床应用。
