title: 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.
abstract: OBJECTIVE
  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.
  
  
  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, β1- and α6-integrins (ITΒ1, 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, α6 integrin; 1.26±0.53, β1 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Reproductive Biology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nahid Ataie
authors.initials: NA
authors.lastname: Nejad
authors.affiliation: Department of Anatomical Sciences, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fardin
authors.initials: F
authors.lastname: Amidi
authors.affiliation: IVF Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Marziyeh Agha
authors.initials: MA
authors.lastname: Hoseini
authors.affiliation: Institute for Molecular Medicine and Cell Therapy, Düsseldorf, Germany and GENEOCELL, Advanced Molecular & Cellular Technologies, Tehran, Iran.
authors.forename: Karim Nayer
authors.initials: KN
authors.lastname: Nia
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
authors.forename: Mehryar
authors.initials: M
authors.lastname: Habibi
authors.affiliation: Pediatric Urology Research Center, Children Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abdol Mohammad
authors.initials: AM
authors.lastname: Kajbafzadeh
authors.affiliation: Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Mazaheri
authors.affiliation: Department of Reproductive Biology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nazila
authors.initials: N
authors.lastname: Yamini
keywords: Mesenchymalstem cell; PGC; Placenta; Spermatogonial stem cell; Wharton’s jelly