Reprogramming of adult human testicular cells by four transcription factors (OCT4, SOX2, KLF4, and C-MYC).

PURPOSE: Induced pluripotent stem (iPS) cells have been generated from mouse and human fibroblasts by several groups; however, transplanted mouse iPS cells can cause teratomas, depending on their tissue of origin. Therefore, human iPS cells are preferable, and various tissues are being evaluated for their potential to generate human iPS cells. METHODS: We examined whether adult human testicular tissue had undergone reprogramming by introducing four transcription factors, OCT4, SOX2, KLF4, and C-MYC, using lentiviral vectors. RESULTS: We obtained embryonic stem (ES)-like cells derived from human testicular tissue by introducing four cDNAs, encoding the transcription factors OCT4, SOX2, KLF4, and C-MYC, using lentiviral vectors. We showed that DAZL and VASA were expressed in testicular cells but down-regulated in ES-like cells, indicating that the cells had undergone reprogramming. ES-like cells could develop tumors, which is a hallmark of pluripotency, when SCID mice were injected with these cells. CONCLUSIONS: We induced iPS cells from adult human testicular tissue by introducing four transcription factors, OCT4, SOX2, KLF4, and C-MYC, using lentiviral vectors. Future studies on these cells may elucidate the causes of male infertility, and eventually lead to treatments with autologous testicular tissue-derived iPS cells.