Open AccessAll‐trans retinoic acid preconditioning enhances proliferation, angiogenesis and migration of mesenchymal stem cell in vitro and enhances wound repair in vivo
Author(s) -
Pourjafar M.,
Saidijam M.,
Mansouri K.,
Ghasemibasir H.,
Karimi dermani F.,
Najafi R.
Publication year - 2017
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12315
Subject(s) - mesenchymal stem cell , angiogenesis , wound healing , cancer research , pharmacology , vascular endothelial growth factor , in vivo , stem cell , cxcr4 , chemokine , immunology , biology , chemistry , microbiology and biotechnology , inflammation , vegf receptors
Abstract 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 ( MSC s) in vitro and in a wound‐healing model. Materials and methods MSC s 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 ( CXCR 4), C‐C chemokine receptor type 2 ( CCR 2), vascular endothelial growth factor ( VEGF ), angiopoietin‐2 (Ang‐2) and Ang‐4 were examined by qRT ‐ PCR . Prostaglandin E2 ( PGE 2) levels were measured using an ELISA kit and MSC angiogenic potential was evaluated using three‐dimensional tube formation assay. Finally, benefit of ATRA ‐treated MSC s in wound healing was determined with a rat excisional wound model. Results In ATRA ‐treated MSC s, expressions of COX ‐2, HIF ‐1, CXCR 4, CCR 2, 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 MSC s were also significantly enhanced compared to untreated MSC s. Conclusion Pre‐conditioning of MSC s with ATRA increased efficacy of cell therapy by activation of survival signalling pathways, trophic factors and release of pro‐angiogenic molecules.