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 BMP۴ 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 BMP۴, retinoic acid (RA) or co-cultured on human amniotic epithelial (HAE) and chorionic plate (HCP) placenta feeder cells. profile of POU۵F۱, Fragilis, Plzf, DDX۴, Piwil۲, Stra۸, Dazl, β۱- and α۶-integrins (ITΒ۱, ITA۶) genes expression as germ cell markers were analyzed using RT-PCR and real-time PCR. Immunocytochemistry of surface markers were conducted. Results: After ۳ 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 BMP۴ + RA. Induction of hWJ-MSCs with BMP۴ in presence of RA resulted in significant up-regulation (P≤۰.۰۵) of all germ cell specific genes (c-Kit; ۲.۸۴±۰.۵۹, DDX۴; ۱.۶۹±۰.۳۹, Piwil۲; ۱.۱۴±۰.۲۱, Dazl; ۰.۶۵±۰.۲۵, α۶ integrin; ۱.۲۶±۰.۵۳, β۱ integrins; ۱.۱۸±۰.۶۵) 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.

کلیدواژه ها:

Mesenchymal stem cell ، PGC ، Placenta ، Spermatogonial stem cell ، Wharton’s jelly