title: All-trans retinoic acid preconditioning enhances proliferation, angiogenesis and migration of mesenchymal stem cell in vitro and enhances wound repair in vivo.
abstract: OBJECTIVE
  Stem cell therapy is considered to be a suitable alternative in treatment of a number of diseases. However, there are challenges in their clinical application in cell therapy, such as to reduce survival and loss of transplanted stem cells. It seems that chemical and pharmacological preconditioning enhances their therapeutic efficacy. In this study, we investigated effects of all-trans retinoic acid (ATRA) on survival, angiogenesis and migration of mesenchymal stem cells (MSCs) in vitro and in a wound-healing model.
  
  
  METHODS
  MSCs were treated with a variety of concentrations of ATRA, and mRNA expression of cyclo-oxygenase-2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), C-C chemokine receptor type 2 (CCR2), vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and Ang-4 were examined by qRT-PCR. Prostaglandin E2 (PGE2) levels were measured using an ELISA kit and MSC angiogenic potential was evaluated using three-dimensional tube formation assay. Finally, benefit of ATRA-treated MSCs in wound healing was determined with a rat excisional wound model.
  
  
  RESULTS
  In ATRA-treated MSCs, expressions of COX-2, HIF-1, CXCR4, CCR2, VEGF, Ang-2 and Ang-4 increased compared to control groups. Overexpression of the related genes was reversed by celecoxib, a selective COX-2 inhibitor. Tube formation and in vivo wound healing of ATRA-treated MSCs were also significantly enhanced compared to untreated MSCs.
  
  
  CONCLUSIONS
  Pre-conditioning of MSCs with ATRA increased efficacy of cell therapy by activation of survival signalling pathways, trophic factors and release of pro-angiogenic molecules.
authors.affiliation: Research Center for Molecular Medicine, Hamedan University of Medical Sciences, Hamedan, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Pourjafar
authors.affiliation: Research Center for Molecular Medicine, Hamedan University of Medical Sciences, Hamedan, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Saidijam
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical, Sciences, Kermanshah, Iran.
authors.forename: K
authors.initials: K
authors.lastname: Mansouri
authors.affiliation: Department of Pathology, Hamedan University of Medical Sciences, Hamedan, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Ghasemibasir
authors.affiliation: Research Center for Molecular Medicine, Hamedan University of Medical Sciences, Hamedan, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Karimi Dermani
authors.affiliation: Research Center for Molecular Medicine, Hamedan University of Medical Sciences, Hamedan, Iran.|Endometrium and Endometriosis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: R
authors.initials: R
authors.lastname: Najafi
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005269:Femur / Q000166:cytology; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C514936:CXCR4 protein, mouse; D052246:Cyclooxygenase 2 Inhibitors; D051793:Hypoxia-Inducible Factor 1; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D014212:Tretinoin; D051546:Cyclooxygenase 2
keywords: All-trans retinoic acid; cyclooxygenase-2; mesenchymal stem cells; prostaglandin E2; stem cell therapy