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Cartilage repair using an in vitro generated scaffold-free tissue-engineered construct derived from porcine synovial mesenchymal stem cells
Authors:Ando Wataru  Tateishi Kosuke  Hart David A  Katakai Daisuke  Tanaka Yoshinari  Nakata Ken  Hashimoto Jun  Fujie Hiromichi  Shino Konsei  Yoshikawa Hideki  Nakamura Norimasa
Affiliation:

aDepartment of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan

bMcCaig Centre for Joint Injury and Arthritis Research, Faculty of Medicine, University of Calgary, Calgary, Canada

cBiomechanics Laboratory, Department of Mechanical Engineering, Kogakuin University, Tokyo, Japan

Abstract:The objective was to in vitro generate a mesenchymal stem cell (MSC)-based tissue-engineered construct (TEC) to facilitate in vivo repair in a porcine chondral defect model. Porcine synovial MSCs were cultured in monolayer at high density and were subsequently detached from the substratum. The cell/matrix complex spontaneously contracted to develop a basic TEC. Immunohistochemical analysis showed that the basic TEC contained collagen I and III, fibronectin, and vitronectin. The basic TEC exhibited stable adhesion to the surface of a porcine cartilage matrix in an explant culture system. The TEC cultured in chondrogenic media exhibited elevated expression of glycosaminoglycan and chondrogenic marker genes. The TEC were implanted in vivo into chondral defects in the medial femoral condyle of 4-month-old pigs, followed by sacrifice after 6 months. Implantation of a TEC into chondral defects initiated repair with a chondrogenic-like tissue, as well as secure biological integration to the adjacent cartilage. Histologically, the repair tissue stained positively with Safranin O and for collagen II. Biomechanical evaluation revealed that repair tissue exhibited mechanical properties similar to those of normal porcine cartilage in static compression and friction tests. This technology is a unique and promising method for stem cell-based cartilage repair.
Keywords:Cartilage tissue engineering   Mesenchymal stem cell   Animal model   Cell culture   Connective tissue   ECM (extracellular matrix)
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