Department of Orthopaedics, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan.
Biomaterials. 2010 Nov;31(31):8004-11. doi: 10.1016/j.biomaterials.2010.07.017. Epub 2010 Jul 31.
One of the potential factors that may affect the results of mesenchymal stem cell (MSC)-based therapy is the age of donors and recipients. However, there have been no controlled studies to investigate the influence of skeletal maturity on the MSC-based repair of cartilage. The purpose of this study was to compare the repair quality of damaged articular cartilage treated by a scaffold-free three-dimensional tissue-engineered construct (TEC) derived from synovial MSCs between immature and mature pigs. Synovial MSCs were isolated from immature and mature pigs and the proliferation and chondrogenic differentiation capacities were compared. The TEC derived from the synovial MSCs were then implanted into equivalent chondral defects in the medial femoral condyle of both immature and mature pigs, respectively. The implanted defects were morphologically and biomechanically evaluated at 6 months postoperatively. There was no skeletal maturity-dependent difference in proliferation or chondrogenic differentiation capacity of the porcine synovial MSCs. The TEC derived from synovial MSCs promoted the repair of chondral lesion in both immature and mature pigs without the evidence of immune reaction. The repaired tissue by the TEC also exhibited similar viscoelastic properties to normal cartilage regardless of the skeletal maturity. The results of the present study not only suggest the feasibility of allogenic MSC-based cartilage repair over generations but also may validate the use of immature porcine model as clinically relevant to test the feasibility of synovial MSC-based therapies in chondral lesions.
影响间充质干细胞(MSC)治疗效果的一个潜在因素可能是供体和受体的年龄。然而,目前还没有对照研究来调查骨骼成熟度对基于 MSC 的软骨修复的影响。本研究的目的是比较来源于滑膜 MSC 的无支架三维组织工程构建体(TEC)治疗受损关节软骨的修复质量,该 TEC 分别在未成熟和成熟猪之间。从未成熟和成熟猪的滑膜中分离 MSC,并比较其增殖和软骨分化能力。然后将来源于滑膜 MSC 的 TEC 分别植入未成熟和成熟猪内侧股骨髁的等效软骨缺损部位。术后 6 个月对植入的缺损部位进行形态学和生物力学评估。猪滑膜 MSC 的增殖或软骨分化能力与骨骼成熟度无关。来源于滑膜 MSC 的 TEC 促进了未成熟和成熟猪的软骨损伤修复,没有免疫反应的证据。TEC 修复的组织在弹性方面与正常软骨相似,而与骨骼成熟度无关。本研究的结果不仅表明了同种异体 MSC 为基础的软骨修复在几代人中的可行性,而且还可能验证了使用未成熟的猪模型作为临床相关的方法来测试滑膜 MSC 为基础的疗法在软骨损伤中的可行性。