Human cord blood stem cells generate human cytokeratin 18-negative hepatocyte-like cells in injured mouse liver
Human cord blood stem cells generate human cytokeratin 18-negative hepatocyte-like cells in injured mouse liver
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DOI：
10.1016/s0002-9440(10)62997-5
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发表时间：
2005-08-01
影响因子：
6
通讯作者：
Ott, M
中科院分区：
文献类型：
--
作者：
Sharma, AD;Cantz, T;Ott, M
成人骨髓（BM）细胞分化为非造血细胞是一种罕见的现象。然而，一些报告表明，人脐带血 (hUCB) 来源的细胞在移植到非肥胖糖尿病-严重联合免疫缺陷 (NOD-SCID) 小鼠体内后会产生肝细胞。因此，我们分析了 hUCB 细胞的肝分化潜力，并比较了移植 hUCB 与小鼠 BM 细胞后 5 岁接受者 NOD-SCID 小鼠中新形成的肝细胞样细胞的频率。将来自增强型绿色荧光蛋白转基因或野生型小鼠的 hUCB 细胞或小鼠 BM 的单核细胞制剂移植到亚致死照射的 NOD-SCID 小鼠中。通过四氯化碳损伤诱导肝再生，并进行或不进行随后的肝细胞生长因子处理。通过免疫组织化学和逆转录聚合酶链反应，我们在 hUCB 移植小鼠体内检测到肝细胞样细胞簇。这些细胞表达人白蛋白和 Hep Par 1，但表达小鼠 CK18，表明嵌合肝细胞样细胞的形成。天然荧光显微镜和双免疫荧光未能检测到单次移植的增强型绿色荧光蛋白转基因小鼠BM。跨性别小鼠骨髓移植后，荧光原位杂交很少发现供体来源的肝细胞样细胞。因此，hUCB细胞在移植到NOD-SCID小鼠后具有与鼠BM细胞不同的分化能力，这证明了在hUCB细胞可用于治疗之前进一步测试的重要性。源自移植的增强型绿色荧光蛋白转基因小鼠BM的肝细胞。跨性别小鼠骨髓移植后，荧光原位杂交很少发现供体来源的肝细胞样细胞。因此，hUCB细胞在移植到NOD-SCID小鼠后具有不同于鼠BM细胞的分化能力，这证明了在hUCB细胞用于治疗之前进一步测试的重要性。
Differentiation of adult bone marrow (BM) cells into nonhematopoietic cells is a rare phenomenon. Several reports, however, suggest that human umbilical cord blood (hUCB)-derived cells give rise to hepatocytes after transplantation into nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice. Therefore, we analyzed the hepatic differentiation potential of hUCB cells and compared the frequency of newly formed hepatocyte-like cells in the fivers of recipient NOD-SCID mice after transplantation of hUCB versus murine BM cells. Mononuclear cell preparations of hUCB cells or murine BM from enhanced green fluorescent protein transgenic or wild-type mice were transplanted into sublethally irradiated NOD-SCID mice. Liver regeneration was induced by carbon tetrachloride injury with and without subsequent hepatocyte growth factor treatment. By immunohistochemistry and reverse transcriptase-polymerase chain reaction, we detected clusters of hepatocyte-like cells in the fivers of hUCB-transplanted mice. These cells expressed human albumin and Hep Par 1 but mouse CK18, suggesting the formation of chimeric hepatocyte-like cells. Native fluorescence microscopy and double immunofluorescence failed to detect single transplanted enhanced green fluorescent protein-transgenic mouse BM. Fluorescent in situ hybridization rarely revealed donor-derived hepatocyte-like cells after cross-gender mouse BM transplantation. Thus, hUCB cells have differentiation capabilities different from murine BM cells after transplantation into NOD-SCID mice, demonstrating the importance of further testing before hUCB cells can be used therapeutically.hepatocytes derived from transplanted enhanced green fluorescent protein-transgenic mouse BM. Fluorescent in situ hybridization rarely revealed donor-derived hepatocyte-like cells after cross-gender mouse BM transplantation. Thus, hUCB cells have differentiation capabilities different from murine BM cells after transplantation into NOD-SCID mice, demonstrating the importance of further testing before hUCB cells can be used therapeutically.