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Isolation and Characterization of Pluripotent Human Spermatogonial Stem Cell-Derived Cells
Nina Kossack 1, Juanito Meneses 2, Shai Shefi 3, Ha Nam Nguyen 1, Shawn Chavez 1, Cory Nicholas 1, Joerg Gromoll 4, Paul J Turek 5, Renee A Reijo-Pera 1*
1 Institute for Stem Cell Biology and Regenerative Medicine; Department of Obstetrics and Gynecology; Stanford University School of Medicine, Palo Alto, CA 94304
2 Center for Reproductive Sciences and cDepartment of Urology; University of California San Francisco, San Francisco, CA 94043
3 Department of Urology; University of California San Francisco, San Francisco, CA 94043; Sheba Medical Center; Tel Hashomer 52621, Israel
4 Center of Reproductive Medicine and Andrology, University of Muenster, Domagkstrasse 11, D-48129 Muenster, Germany
5 Department of Urology; University of California San Francisco, San Francisco, CA 94043
Several reports have documented the derivation of pluripotent cells (multipotent germline stem cells (MGSCs)) from spermatogonial stem cells obtained from the adult mouse testis. These spermatogoniaderived stem cells express embryonic stem cell markers and differentiate to the three primary germ layers, as well as the germ line. Data indicates that derivation may involve reprogramming of endogenous spermatogonia in culture. Here, we report the derivation of human multipotent germline stem cells (hMGSCs) from a testis biopsy. The cells express distinct markers of pluripotency, form embryoid bodies that contain derivatives of all three germ layers, maintain a normal XY karyotype, are hypomethylated at the H19 locus and express high levels of telomerase. Teratoma assays indicate the presence of human cells 8-weeks post-transplantation but limited teratoma formation. Thus, these data suggest the potential to derive pluripotent cells from human testis biopsies but indicate a need for novel strategies to optimize hMGSC culture conditions and reprogramming.