Research Papers:
Transdifferentiation of human male germline stem cells to hepatocytes in vivo via the transplantation under renal capsules
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Abstract
Zheng Chen1,6,*, Minghui Niu1,*, Min Sun1,*, Qingqing Yuan1,*, Chencheng Yao1, Jingmei Hou1, Hong Wang1, Liping Wen1, Hongyong Fu1, Fan Zhou1, Zheng Li2, Zuping He1,3,4,5
1State Key Laboratory of Oncogenes and Related Genes, Renji- Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
2Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
3Shanghai Institute of Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
4Shanghai Key Laboratory of Assisted Reproduction and Reproductive Genetics, Shanghai 200127, China
5Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China
6Department of General Surgery, Suqian people's Hospital, The Affiliated Hospital of Xuzhou Medical University, Jiangsu 223800, China
*These authors contributed equally to this work
Correspondence to:
Zuping He, email: [email protected]
Keywords: human, spermatogonial stem cells, transplantation, in vivo, transdifferentiation
Received: November 25, 2016 Accepted: January 11, 2017 Published: January 18, 2017
ABSTRACT
Here we proposed a new concept that human spermatogonial stem cells (SSCs) can transdifferentiate into hepatocytes in vivo. We first established liver injury model of mice by carbon tetrachloride to provide proper environment for human SSC transplantation. Liver mesenchymal cells were isolated from mice and identified phenotypically. Human SSC line was recombined with liver mesenchymal cells, and they were transplanted under renal capsules of nude mice with liver injury. The grafts expressed hepatocyte hallmarks, including ALB, AAT, CK18, and CYP1A2, whereas germ cell and SSC markers VASA and GPR125 were undetected in these cells, implicating that human SSCs were converted to hepatocytes. Furthermore, Western blots revealed high levels of PCNA, AFP, and ALB, indicating that human SSCs-derived hepatocytes had strong proliferation potential and features of hepatocytes. In addition, ALB–, CK8–, and CYP1A2– positive cells were detected in liver tissues of recipient mice. Significantly, no obvious lesion or teratomas was observed in several important organs and tissues of recipient mice, reflecting that transplantation of human SSCs was safe and feasible. Collectively, we have for the first time demonstrated that human SSCs can be transdifferentiated to hepatocyte in vivo. This study provides a novel approach for curing liver diseases using human SSC transplantation.
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