An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes

An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes
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DOI:
10.1093/jb/mvg173
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发表时间:
2003-10-01
影响因子:
2.7
通讯作者:
Okita, K
Okita, K
中科院分区:
生物学4区
文献类型:
--
作者:
Terai, S;Sakaida, I;Okita, K

文献摘要

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骨髓细胞(BMCs)的可塑性仍然存在争议。目前的研究发现,持续性损伤诱导有效的转分化为功能性肝细胞的骨髓基质细胞。通过尾静脉向四氯化碳诱导的肝硬化小鼠注射1 × 10(5)个未处理的绿色荧光蛋白(GFP)阳性BMC。在这些小鼠中,移植的GFP阳性BMCs在一天后有效地迁移到肝小叶的门静脉周围区域,在4周时重新填充25%的受体肝脏。与此相反,没有GFP阳性的骨髓基质细胞移植到对照小鼠与未受损的肝脏。BMCs通过未成熟的成肝细胞转分化为功能性成熟肝细胞。血清白蛋白水平显着升高,以弥补慢性肝功能衰竭的BMC移植。这些结果表明,受体条件和微环境是使用BMC进行成功细胞治疗的关键因素。
The plasticity of bone marrow cells (BMCs) remains controversial. The present study found that persistent injury induces efficient trans-differentiation of BMCs into functional hepatocytes. Mice with liver cirrhosis induced by carbon tetrachloride were injected with 1 x 10(5) non-treated green fluorescent protein (GFP)-positive BMCs via the tail vein. In these mice, transplanted GFP-positive BMCs efficiently migrated into the peri-portal area of liver lobules after one day, repopulating 25% of the recipient liver by 4 weeks. In contrast, no GFP-positive BMCs were detected following transplantation into control mice with undamaged livers. BMCs trans-differentiated into functional mature hepatocytes via immature hepatoblasts. Serum albumin levels were significantly elevated to compensate for chronic liver failure in BMC transplantation. These results reveal that recipient conditions and microenvironments represent key factors for successful cell therapy using BMCs.