PMID- 27862498 OWN - NLM STAT- MEDLINE DCOM- 20170206 LR - 20231011 IS - 1365-2184 (Electronic) IS - 0960-7722 (Print) IS - 0960-7722 (Linking) VI - 50 IP - 1 DP - 2017 Feb TI - All-trans retinoic acid preconditioning enhances proliferation, angiogenesis and migration of mesenchymal stem cell in vitro and enhances wound repair in vivo. LID - 10.1111/cpr.12315 [doi] LID - e12315 AB - OBJECTIVES: 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. MATERIALS AND 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. CONCLUSION: 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. CI - (c) 2016 John Wiley & Sons Ltd. FAU - Pourjafar, M AU - Pourjafar M AD - Research Center for Molecular Medicine, Hamedan University of Medical Sciences, Hamedan, Iran. FAU - Saidijam, M AU - Saidijam M AD - Research Center for Molecular Medicine, Hamedan University of Medical Sciences, Hamedan, Iran. FAU - Mansouri, K AU - Mansouri K AD - Medical Biology Research Center, Kermanshah University of Medical, Sciences, Kermanshah, Iran. FAU - Ghasemibasir, H AU - Ghasemibasir H AD - Department of Pathology, Hamedan University of Medical Sciences, Hamedan, Iran. FAU - Karimi Dermani, F AU - Karimi Dermani F AD - Research Center for Molecular Medicine, Hamedan University of Medical Sciences, Hamedan, Iran. FAU - Najafi, R AU - Najafi R AD - Research Center for Molecular Medicine, Hamedan University of Medical Sciences, Hamedan, Iran. AD - Endometrium and Endometriosis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. LA - eng SI - GENBANK/NM_017232 SI - GENBANK/NM_024359 SI - GENBANK/NM_022205 SI - GENBANK/NM_021866 SI - GENBANK/NM_001287107 SI - GENBANK/NM_134454 SI - GENBANK/NM_001106526 SI - GENBANK/NR_046237 PT - Journal Article DEP - 20161110 PL - England TA - Cell Prolif JT - Cell proliferation JID - 9105195 RN - 0 (CXCR4 protein, mouse) RN - 0 (Cyclooxygenase 2 Inhibitors) RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (Receptors, CXCR4) RN - 0 (Vascular Endothelial Growth Factor A) RN - 5688UTC01R (Tretinoin) RN - EC 1.14.99.1 (Cyclooxygenase 2) SB - IM MH - Animals MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Cyclooxygenase 2/chemistry/genetics/metabolism MH - Cyclooxygenase 2 Inhibitors/pharmacology MH - Enzyme Activation/drug effects MH - Femur/cytology MH - Hypoxia-Inducible Factor 1/genetics/metabolism MH - Male MH - Mesenchymal Stem Cells/*cytology/*drug effects/metabolism MH - Neovascularization, Physiologic/*drug effects MH - Rats MH - Rats, Wistar MH - Receptors, CXCR4/genetics/metabolism MH - Signal Transduction/drug effects MH - Skin/pathology MH - Tretinoin/*pharmacology MH - Vascular Endothelial Growth Factor A/genetics/metabolism MH - Wound Healing/*drug effects PMC - PMC6529123 OTO - NOTNLM OT - All-trans retinoic acid OT - cyclooxygenase-2 OT - mesenchymal stem cells OT - prostaglandin E2 OT - stem cell therapy COIS- The authors declare no conflict of interests related to this study. EDAT- 2016/11/20 06:00 MHDA- 2017/02/07 06:00 PMCR- 2016/11/10 CRDT- 2016/11/19 06:00 PHST- 2016/08/04 00:00 [received] PHST- 2016/10/10 00:00 [accepted] PHST- 2016/11/20 06:00 [pubmed] PHST- 2017/02/07 06:00 [medline] PHST- 2016/11/19 06:00 [entrez] PHST- 2016/11/10 00:00 [pmc-release] AID - CPR12315 [pii] AID - 10.1111/cpr.12315 [doi] PST - ppublish SO - Cell Prolif. 2017 Feb;50(1):e12315. doi: 10.1111/cpr.12315. Epub 2016 Nov 10.