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

• Published in: Biomaterials Vol. 64; pp. 88 - 97
• Main Authors: Zhang, Ying, Pizzute, Tyler, Li, Jingting, He, Fan, Pei, Ming
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-09-2015
• Subjects: Adult; Adult Stem Cells - drug effects; Advanced Basic Science; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biomedical materials; Cartilage; Cartilage - pathology; Cartilage - physiology; Cells, Cultured; Chondrogenesis - drug effects; Chondrogenic potential; Culture Media - pharmacology; Decellularized extracellular matrix; Dentistry; Drug Evaluation, Preclinical; Extracellular Matrix; Female; HLA-DR Antigens - analysis; Humans; Imidazoles - pharmacology; In Vitro Techniques; Inflammation; Inhibitors; Interleukin-1 beta; Interleukin-1beta - pharmacology; Male; Mesenchymal stem cell; Osteoarthritis - drug therapy; p38 MAPK inhibitor; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; Patients; Preconditioning; Protein Kinase Inhibitors - pharmacology; Pyridines - pharmacology; Regeneration; Regeneration - drug effects; Rejuvenation; Stem cells; Surgical implants; Synovial Membrane - cytology; Transplantation, Autologous; Mesenchymal stem cell; Decellularized extracellular matrix; Chondrogenic potential; Preconditioning; p38 MAPK inhibitor; Interleukin-1 beta
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2015.06.038

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.