title: Epac Activation Regulates Human Mesenchymal Stem Cells Migration and Adhesion.
abstract: How to enhance the homing of human mesenchymal stem cells (hMSCs) to the target tissues remains a clinical challenge nowadays. To overcome this barrier, the mechanism responsible for the hMSCs migration and engraftment has to be defined. Currently, the exact mechanism involved in migration and adhesion of hMSCs remains unknown. Exchange protein directly activated by cAMP (Epac), a novel protein discovered in cAMP signaling pathway, may have a potential role in regulating cells adhesion and migration by triggering the downstream Rap family signaling cascades. However, the exact role of Epac in cells homing is elusive. Our study evaluated the role of Epac in the homing of hMSCs. We confirmed that hMSCs expressed functional Epac and its activation enhanced the migration and adhesion of hMSCs significantly. The Epac activation was further found to be contributed directly to the chemotactic responses induced by stromal cell derived factor-1 (SDF-1) which is a known chemokine in regulating hMSCs homing. These findings suggested Epac is connected to the SDF-1 signaling cascades. In conclusion, our study revealed that Epac plays a role in hMSCs homing by promoting adhesion and migration. Appropriate manipulation of Epac may enhance the homing of hMSCs and facilitate their future clinical applications.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong Special Administration Region, People's Republic of China.|Beijing Children's Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Jiao-Le
authors.initials: JL
authors.lastname: Yu
authors.affiliation: Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong Special Administration Region, People's Republic of China.
authors.forename: Ruixia
authors.initials: R
authors.lastname: Deng
authors.affiliation: Department of Ophthalmology, School of Biomedical Sciences, The University of Hong Kong, Hong Kong Special Administration Region, People's Republic of China.|State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong Special Administration Region, People's Republic of China.
authors.forename: Sookja K
authors.initials: SK
authors.lastname: Chung
authors.affiliation: Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong Special Administration Region, People's Republic of China.|Center for Cancer Research, The University of Hong Kong, Hong Kong Special Administration Region, People's Republic of China.|Stem Cell & Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administration Region, People's Republic of China.
authors.forename: Godfrey Chi-Fung
authors.initials: GC
authors.lastname: Chan
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D054377:Chemokine CXCL12 / Q000096:biosynthesis* / Q000235:genetics; D000242:Cyclic AMP / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D020662:Guanine Nucleotide Exchange Factors; C116122:RAPGEF3 protein, human; D000242:Cyclic AMP
keywords: Cell migration; Marrow stromal stem cells; Mesenchymal stem cells; SDF-1