Differentiation Of Human Umbilical Cord Wharton's Jelly -Derived Mesenchymal Stem Cells Into Male Germ Cells

[BACKGROUND & AIM] Male infertility caused by germ cell deficient seems to be hard to cure by traditional assisted reproductive technology, however, this obstacle now has been break through by germ cell transplantation in resent years. Human umbilical cord wharton's jelly-derived mesenchymal stem cells (HUMSCs) possess pluripotent characteristics for indefinite proliferation and can be induced to differentiate into advanced derivatives of all three germ layers. Our previous study have shown that HUMSCs present some germ cell characteristics after induction in vitro, there was no immunological rejection after transplanted to infertility male mice, HUMSCs migrated in seminiferous tubule and was still survive after 120 days. This research will made a further study to investigate the male germ cell differentiation potential of HUMSCs, and its biological characteristics in vitro and in vivo.[MATERIALS & METHODS] HUMSCs was isolated and expanded by tissue adherent culture, the pluripotent characteristics of HUMSCs was detected by flow cytometry, and HUMSCs was curtured in all-trans retinoic acid, testosterone testicular-cell-conditioned medium prepared from newborn male mouse testes. Characteristics of HUMSC-derived germ-like cells were observed by morphology, and expression of germ-cell-specific markers in differentiated cells were analyzed by RT-PCR and immunocytochemistry. HUMSCs were transplanted into seminiferous tubule of infertility male mice, and human male germ cell related markers expressed in receptor mice were detected by RT-PCR.[RESULT] HUMSCs expanded in vitro showed a high expression of MSC markers such as Oct4, CD29, CD44, and CD59. They formed "tadpole-like" cells after 7days of induction with different reagents, and showed both mRNA and protein expression of germ-cell-specific markers Oct4 (POUF5), Ckit, CD49f(a6), Stella (DDPA3) at day 3 and 7, Vasa (DDX4) was expressed at day 14. RT-PCR shown that the teste of infertility male mice was expressed human male germ cell markers Stella (DDPA3) and Dazl after 1 month HUMSCs transplantation.[CONCLUSION] The mesenchymal stem cells derived from human umbilical cord wharton's jelly have the potential to differentiate into male germ cell in vitro and in vivo. HUMSCs could be a promising source of cell transplantation therapy and provide a new route for infertilitas therapy.