title: Platelet rich plasma clot releasate preconditioning induced PI3K/AKT/NFκB signaling enhances survival and regenerative function of rat bone marrow mesenchymal stem cells in hostile microenvironments.
abstract: Mesenchymal stem cells (MSCs) have been optimal targets in the development of cell based therapies, but their limited availability and high death rate after transplantation remains a concern in clinical applications. This study describes novel effects of platelet rich clot releasate (PRCR) on rat bone marrow-derived MSCs (BM-MSCs), with the former driving a gene program, which can reduce apoptosis and promote the regenerative function of the latter in hostile microenvironments through enhancement of paracrine/autocrine factors. By using reverse transcription-polymerase chain reaction, immunofluorescence and western blot analyses, we showed that PRCR preconditioning could alleviate the apoptosis of BM-MSCs under stress conditions induced by hydrogen peroxide (H2O2) and serum deprivation by enhancing expression of vascular endothelial growth factor and platelet-derived growth factor (PDGF) via stimulation of the platelet-derived growth factor receptor (PDGFR)/PI3K/AKT/NF-κB signaling pathways. Furthermore, the effects of PRCR preconditioned GFP-BM-MSCs subcutaneously transplanted into rats 6 h after wound surgery were examined by histological and other tests from days 0-22 after transplantation. Engraftment of the PRCR preconditioned BM-MSCs not only significantly attenuated apoptosis and wound size but also improved epithelization and blood vessel regeneration of skin via regulation of the wound microenvironment. Thus, preconditioning with PRCR, which reprograms BM-MSCs to tolerate hostile microenvironments and enhance regenerative function by increasing levels of paracrine factors through PDGFR-α/PI3K/AKT/NF-κB signaling pathways would be a safe method for boosting the effectiveness of transplantation therapy in the clinic.
authors.affiliation: 1 The Key Laboratory of Trauma Treatment & Tissue Repair of Tropical Area, PLA, Department of Plastic Surgery, Guangzhou General Hospital of Guangzhou Command , Guangzhou, People's Republic of China .
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.forename: Sha
authors.initials: S
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Biao
authors.initials: B
authors.lastname: Cheng
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Nie
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liu
authors.forename: Kui
authors.initials: K
authors.lastname: Ma
authors.forename: Jiping
authors.initials: J
authors.lastname: Zhou
authors.forename: Dongyun
authors.initials: D
authors.lastname: Gao
authors.forename: Changjiang
authors.initials: C
authors.lastname: Feng
authors.forename: Siming
authors.initials: S
authors.lastname: Yang
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics / Q000628:therapy*; D016328:NF-kappa B / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D053657:Platelet-Rich Plasma / Q000737:chemistry*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D055153:Stem Cell Niche / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000097:blood
chemical_list: D017077:Culture Media, Conditioned; D016328:NF-kappa B; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt