title: Bone regeneration in a massive rat femur defect through endochondral ossification achieved with chondrogenically differentiated MSCs in a degradable scaffold.
abstract: Mesenchymal stem cells (MSCs) are multipotent cells capable of proliferating and differentiating into several lineages. In regenerative medicine, their potential as a resource for tissue-replacement therapy is receiving much attention. However, transplanting MSCs to repair larger bone defects in animal models has so far proved disappointing. Here we report on the healing of both critical-sized (5 mm) and massive (15 mm) full-thickness femur defects in rats by implanting a uniquely fabricated PLGA scaffold seeded with MSCs pre-differentiated in vitro into cartilage-forming chondrocytes (MSC-DCs). This strategy closely mimics endochondral ossification, the process by which long bones develop in nature. It is thought that because the transplanted MSC-DCs induced natural bone formation, the defect size was not critical to the outcome. Crucially, after 8 weeks the mean biomechanical strength of femora with the massive 15 mm implant reached 75% that of a normal rat femur, while in the case of 5 mm implants there was no significant difference. Successful healing was also highly reproducible, with bone union occurring in all treated animals examined radiologically 8 or 16 weeks after surgery.
authors: Department of Orthopaedic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8606, Japan. Electronic address: norinori830214@yahoo.co.jp.
authors: Noriko
authors: N
authors: Harada
authors: Department of Orthopaedic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8606, Japan.
authors: Yoshinobu
authors: Y
authors: Watanabe
authors: Department of Orthopaedic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8606, Japan.
authors: Kenji
authors: K
authors: Sato
authors: Department of Orthopaedic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8606, Japan.
authors: Satoshi
authors: S
authors: Abe
authors: GC Corporation, 76-1, Hasunuma-cho, Itabashi-ku, Tokyo 174-8585, Japan.
authors: Katsuyuki
authors: K
authors: Yamanaka
authors: GC Corporation, 76-1, Hasunuma-cho, Itabashi-ku, Tokyo 174-8585, Japan.
authors: Yuhiro
authors: Y
authors: Sakai
authors: GC Corporation, 76-1, Hasunuma-cho, Itabashi-ku, Tokyo 174-8585, Japan.
authors: Tadashi
authors: T
authors: Kaneko
authors: Department of Orthopaedic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8606, Japan.
authors: Takashi
authors: T
authors: Matsushita
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001861:Bone Regeneration; D002454:Cell Differentiation; D020219:Chondrogenesis; D003094:Collagen / Q000378:metabolism; D016267:External Fixators; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D005455:Fluorescent Antibody Technique; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011916:Rats, Inbred F344; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen
keywords: Bone regeneration; Bone tissue engineering; Chondrocytes; Copolymer; Mesenchymal stem cell; Scaffold