Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells.
Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells.
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DOI：
10.1182/blood-2002-05-1338
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发表时间：
2003-05
期刊：
影响因子：
20.3
通讯作者：
Xiuli Wang;S. Ge;G. McNamara;Q. Hao;G. Crooks;J. Nolta
中科院分区：
文献类型：
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作者：
Xiuli Wang;S. Ge;G. McNamara;Q. Hao;G. Crooks;J. Nolta
啮齿类动物的骨髓细胞可以为肝脏做贡献。如果这些发现适用于人类，理论上可以从患者身上获得骨髓干细胞，并用于修复他/她受损的肝脏。为了探索这种潜力，将来自脐带血和骨髓的CD 34（+）或高度纯化的CD 34（+）CD 38（-）CD 7（-）人造血干细胞移植到免疫缺陷小鼠中。移植后1个月，给予小鼠四氯化碳（CCl（4））诱导肝损伤和肝细胞增殖。在肝损伤后一个月，将CCl（4）损伤的小鼠与未接受移植的小鼠和接受相同干细胞群移植的未损伤对照小鼠进行比较。小鼠肝脏中表达人特异性白蛋白mRNA和蛋白质，在CCl（4）损伤小鼠的血清中检测到人白蛋白。人甲胎蛋白从未表达，但在一些小鼠中，人细胞角蛋白19表达，这可能表明除了白蛋白分泌肝细胞样细胞外，胆管发育。人白蛋白在未接受移植的受伤小鼠的起始干细胞群中不表达，也不在接受人干细胞移植的未受伤小鼠中表达。人白蛋白表达仅在接受人干细胞移植的CCl（4）处理小鼠中检测到，并且在CCl（4）介导的肝损伤后48小时给予人肝细胞生长因子可增加恢复。我们的研究提供的证据表明，人类“造血”干/祖细胞群体有能力通过诱导白蛋白表达来响应受损的肝脏微环境。
Rodent bone marrow cells can contribute to liver. If these findings are applicable to humans, marrow stem cells could theoretically be harvested from a patient and used to repair his/her damaged liver. To explore this potential, CD34(+) or highly purified CD34(+)CD38(-)CD7(-) human hematopoietic stem cells from umbilical cord blood and bone marrow were transplanted into immunodeficient mice. One month after transplantation, carbon tetrachloride (CCl(4)) was administered into the mice to induce liver damage and hepatocyte proliferation. Mice were analyzed in comparison with CCl(4)-injured mice that did not receive transplants and noninjured controls that received transplants with the same stem cell populations, one month after liver damage. Human-specific albumin mRNA and protein were expressed in the mouse liver and human albumin was detected in the serum of mice that had received CCl(4) injury. Human alpha-fetoprotein was never expressed, but in some mice, human cytokeratin 19 was expressed, which may indicate bile duct development in addition to the albumin-secreting hepatocyte-like cells. Human albumin was not expressed in the starting stem cell populations in injured mice that did not receive transplants nor in noninjured mice that had received transplants of human stem cells. Human albumin expression was detected only in CCl(4)-treated mice that received transplants of human stem cells, and recovery was increased by administration of human hepatocyte growth factor 48 hours after the CCl(4)-mediated liver injury. Our studies provide evidence that human "hematopoietic" stem/progenitor cell populations have the capacity to respond to the injured liver microenvironment by inducing albumin expression.