Male germ-like cell differentiation potential of human umbilical cord Wharton's jelly-derived mesenchymal stem cells in co-culture with human placenta cells in presence of BMP4 and retinoic acid

Objective(s): Mesenchymal stem cells (MSCs) derived from Wharton's jelly (WJ-MSCs) are now much more appealing for cell-based infertility therapy. Hence, WJ-MSCs differentiation toward germ layer cells for cell therapy purposes is currently under intensive study. Materials and Methods: MSCs were isolated from human Wharton's jelly and treated with BMP4, retinoic acid (RA) or co-cultured on human amniotic epithelial (HAE) and chorionic plate (HCP) placenta feeder cells. profile of POU5F1, Fragilis, Plzf, DDX4, Piwil2, Stra8, Dazl, beta 1-and alpha 6-integrins (ITB1, ITA6) genes expression as germ cell markers were analyzed using RT-PCR and real-time PCR. Immunocytochemistry of surface markers were conducted. Results: After 3 weeks treatment with different reagents and co-culture system, morphology of WJ-MSCs changed to shiny clusters and germ cell specific markers in mRNA were up-regulated in both placental feeder + RA and BMP4 + RA. Induction of hWJ-MSCs with BMP4 in presence of RA resulted in significant up-regulation (P <= 0.05) of all germ cell specific genes (c-Kit; 2.84 +/- 0.59, DDX4; 1.69 +/- 0.39, Piwil2; 1.14 +/- 0.21, Dazl; 0.65 +/- 0.25, alpha 6 integrin; 1.26 +/- 0.53, beta 1 integrins; 1.18 +/- 0.65) compared to control and placental feeder cells + RA. Our results indicated that HAE and HCP followed by RA treatment were involved in human germ cell development. Conclusion: We demonstrated that under the right conditions, hWJ-MSCs have the ability to differentiate to germ cells and this provides an excellent pattern to study infertility cause and treatment.