Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion
Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion
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DOI：
10.1182/blood-2005-02-0572
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发表时间：
2005-07-15
期刊：
影响因子：
20.3
通讯作者：
Niitsu, Y
中科院分区：
文献类型：
--
作者：
Sato, Y;Araki, H;Niitsu, Y
骨髓细胞的肝转分化先前已经通过静脉内给予供体细胞而得到证实，供体细胞在受体骨髓中经历增殖和分化后可以再循环到肝脏。在本研究中，为了阐明人骨髓中哪些细胞成分更有效地分化为肝细胞，我们将人骨髓细胞分为间充质干细胞（MSC）、CD 34（+）细胞和非MSC/CD 34（-）细胞，并通过直接异种移植到烯丙醇（AA）处理的大鼠肝脏中进行检查。肝细胞样细胞，如所揭示的阳性免疫染色的人特异性甲胎蛋白（AFP），白蛋白（Alb），细胞角蛋白19（CK 19），细胞角蛋白18（CK 18），和去唾液酸糖蛋白受体（AGPR），并通过逆转录-聚合酶链反应（RTPCR）的表达AFP和Alb mRNA，只在受体肝脏与MSC馏分。细胞融合不太可能参与，因为人类和大鼠的染色体是独立的荧光原位杂交（FISH）确定。分化似乎遵循肝个体发育的过程，MSC基因组中基因表达的重编程，如在早期阶段AFP基因和在后期阶段白蛋白基因的表达所证明的。总之，我们已经证明，骨髓间充质干细胞是最有效的组成部分，在肝分化，揭示了直接异种移植到大鼠肝脏。
Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34(+) cells, and non-MSCs/ CD34(-) cells and examined them by directly xenografting to allylalcohol (AA)- treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18), and asialoglycoprotein receptor (AGPR), and by reverse transcription-polymerase chain reaction (RTPCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (FISH). The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the albumin gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat livers.