title: sb203580 preconditioning recharges matrix-expanded human adult stem cells for chondrogenesis in an inflammatory environment - A feasible approach for autologous stem cell based osteoarthritic cartilage repair.
abstract: Autologous stem cells are a promising cell source for cartilage regeneration; however, cell replicative senescence and joint posttraumatic inflammation provide challenges in bringing this treatment modality to fruition. In this study, we hypothesized that preconditioning with p38 MAPK inhibitor (sb203580) would recharge decellularized extracellular matrix (dECM) expanded human synovium-derived stem cell (hSDSC) chondrogenesis in an inflammatory environment. We found that preconditioning with sb203580 greatly enhanced dECM expanded hSDSC proliferation and chondrogenic potential while supplementation with sb203580 in an induction medium dramatically retarded hSDSC chondrogenic differentiation, even for dECM expanded cells. We also found that sb203580 preconditioning enhanced matrix-expanded hSDSC chondrogenic capacity even in an interleukin-1 (IL-1) induced inflammatory environment. Non-detectable expression of HLA-DR in the hSDSCs grown on allogeneic dECM indicates the feasibility of commercial preparation of these dECMs from healthy, young donors for patients who need autologous transplantation. Our study indicated that p38 MAPK inhibitor has a distinctive priming effect on dECM mediated stem cell cartilage regeneration. Combined rejuvenation with sb203580 and dECM expansion can precondition hSDSCs' resurfacing capacity for osteoarthritic patients with cartilage defects.
authors.affiliation: Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV 26506, USA; Mechanical and Aerospace Engineering, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV 26506, USA; Exercise Physiology, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Pizzute
authors.affiliation: Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV 26506, USA; Exercise Physiology, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Jingting
authors.initials: J
authors.lastname: Li
authors.affiliation: Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV 26506, USA; Exercise Physiology, West Virginia University, Morgantown, WV 26506, USA; Orthopaedic Institute, Soochow University, Suzhou 215007, China.
authors.forename: Fan
authors.initials: F
authors.lastname: He
authors.affiliation: Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV 26506, USA; Mechanical and Aerospace Engineering, West Virginia University, Morgantown, WV 26506, USA; Exercise Physiology, West Virginia University, Morgantown, WV 26506, USA. Electronic address: mpei@hsc.wvu.edu.
authors.forename: Ming
authors.initials: M
authors.lastname: Pei
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000187:drug effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002356:Cartilage / Q000473:pathology / Q000502:physiology; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects*; D003470:Culture Media / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005109:Extracellular Matrix; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007249:Inflammation; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D010003:Osteoarthritis / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D012038:Regeneration / Q000187:drug effects; D012060:Rejuvenation; D013583:Synovial Membrane / Q000166:cytology*; D014182:Transplantation, Autologous; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003470:Culture Media; D006684:HLA-DR Antigens; D007093:Imidazoles; D053583:Interleukin-1beta; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: Chondrogenic potential; Decellularized extracellular matrix; Interleukin-1 beta; Mesenchymal stem cell; Preconditioning; p38 MAPK inhibitor