Human cord blood CD34 cells develop into hepatocytes in the livers of NOD/SCID/ (cid:2) cnull mice through cell fusion
Human cord blood CD34 cells develop into hepatocytes in the livers of NOD/SCID/ (cid:2) cnull mice through cell fusion
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发表时间：
2007
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通讯作者：
Hisanori Fujino;H. Hiramatsu;A. Tsuchiya;A. Niwa;H. Noma;M. Shiota;K. Umeda;M. Yoshimoto;Mamoru Ito;T. Heike;T. Nakahata
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作者：
Hisanori Fujino;H. Hiramatsu;A. Tsuchiya;A. Niwa;H. Noma;M. Shiota;K. Umeda;M. Yoshimoto;Mamoru Ito;T. Heike;T. Nakahata
一些研究表明，肝细胞可以从造血干细胞产生，但这种情况被认为是罕见的，需要肝脏损伤。为了研究人类细胞中的这种现象，我们使用了NOD/SCID/(CID：2)cull(NOG)小鼠模型，当移植到人类造血细胞时，可以达到非常高的嵌合体水平。NOG小鼠静脉注射人白蛋白和(CID：3)-1-抗胰蛋白酶阳性细胞后，即使未经肝毒性治疗，仍能在肝脏内检测到人白蛋白和(CID：3)-1-抗胰蛋白酶阳性细胞。人脐血CD34(CID：1)细胞移植。在小鼠血清中检测到人白蛋白，表明人肝细胞功能成熟。对单细胞悬液中的受体肝细胞进行的流式细胞术分析表明，人白蛋白阳性细胞对小鼠和人的MHC也呈阳性，而对人CD45则为阴性。对受体肝脏的聚合酶链式反应分析显示，各种各样的人类肝细胞或胆管细胞特异性fic mRNAs的表达。这些结果表明，人CD34(CID：1)细胞与无肝损伤的NOG小鼠肝细胞融合，失去其造血表型，并开始肝细胞特异性fic基因转录。CD34(CID：4)细胞移植后未观察到上述现象。因此，我们的模型揭示了人类造血干/祖细胞分化的一条先前统一的途径。-Fujino，人脐血CD34(Cid：1)细胞通过细胞融合在NOD/SCID/(Cid：2)小鼠的肝脏中发育成肝细胞。FASE B J.21,3499-3510
Several studies have shown that hepatocytes can be generated from hematopoietic stem cells, but this event is believed to be rare and to require hepatic damage. To investigate this phenomenon in human cells, we used a NOD/SCID/ (cid:2) cnull (NOG) mouse model that can achieve a tremendously high level of chimerism when transplanted with human hematopoietic cells. Even without hepatotoxic treat-ment other than irradiation, human albumin and (cid:3) -1-antitrypsin-positive cells were invariably detected in the livers of NOG mice after i.v. transplantation of human cord blood CD34 (cid:1) cells. Human albumin was detected in the murine sera, indicating functional maturation of the human hepatocytes. Flow cytometric analysis of recipient liver cells in single-cell suspension demonstrated that human albumin-positive cells were also positive for both murine and human MHC and were negative for human CD45. PCR analysis of recipient livers revealed the expression of a wide variety of human hepatocyte- or cholangiocyte-specific mRNAs. These results show that human CD34 (cid:1) cells fuse with hepatocytes of NOG mice without liver injury, lose their hematopoietic phenotype, and begin hepatocyte-specific gene transcription. These phenomena were not observed when CD34 (cid:4) cells were transplanted. Thus, our model revealed a previously unidentified pathway of human hematopoietic stem/progenitor cell differ-entiation.—Fujino, Human cord blood CD34 (cid:1) cells develop into hepatocytes in the livers of NOD/SCID/ (cid:2) cnull mice through cell fusion. FASEB J. 21, 3499–3510