Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits
Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits
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DOI：
10.1016/j.joca.2013.07.016
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发表时间：
2013-10-01
影响因子：
7
通讯作者：
Yeh, M. -L.
中科院分区：
文献类型：
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作者：
Chang, N. -J.;Lam, C. -F.;Yeh, M. -L.
目的：修复关节软骨在临床上具有挑战性。我们研究了一种简单、有效且临床可行的基于细胞的治疗方法，使用植入自体内皮祖细胞（EPC）的聚（丙交酯-共-乙交酯）（PLGA）支架，通过一步手术修复兔的全层骨软骨缺损。方法：通过纯化兔的少量外周血获得EPC，将其植入高度多孔、生物相容性的PLGA支架中，即EPC-PLGA，并植入股骨内侧髁骨软骨缺损处。 22 只兔子被随机分为三组之一：空缺陷组 (ED)、仅 PLGA 组或 EPC-PLGA 组。植入后4周和12周对缺损部位进行评估。结果：在测试结束时，只有EPC-PLGA组显示出新的软骨组织发育，具有光滑、透明和完整的关节面。此外，组织学分析显示软骨再生存在明显差异。第4周时，EPC-PLGA组显示出明显更高的TGF-β2和TGF-β3表达、更多的合成糖胺聚糖（GAG）含量以及修复组织中更高程度的骨软骨血管生成。第12周时，EPC-PLGA组表现出透明软骨再生增强，柱状软骨细胞排列正常，SOX9表达较高，GAG和II型胶原（COLII）含量较高。此外，EPC-PLGA组表现出有组织的骨软骨整合，形成富含血管的结节骨，单位组织体积的骨体积和小梁厚度（Tb.Th）显着较高。结论：本发明的EPC-PLGA细胞递送系统在不补充外源生长因子的情况下产生了适合骨软骨再生的原位微环境。 (C) 2013 年国际骨关节炎研究协会。由爱思唯尔有限公司出版。保留所有权利。
Objective: Repairing articular cartilage is clinically challenging. We investigated a simple, effective and clinically feasible cell-based therapeutic approach using a poly(lactide-co-glycolide) (PLGA) scaffold seeded with autologous endothelial progenitor cells (EPC) to repair a full-thickness osteochondral defect in rabbits using a one-step surgery.Methods: EPC obtained by purifying a small amount of peripheral blood from rabbits were seeded into a highly porous, biocompatible PLGA scaffold, namely, EPC-PLGA, and implanted into the osteochondral defect in the medial femoral condyle. Twenty two rabbits were randomized into one of three groups: the empty defect group (ED), the PLGA-only group or the EPC-PLGA group. The defect sites were evaluated 4 and 12 weeks after implantation.Results: At the end of testing, only the EPC-PLGA group showed the development of new cartilage tissue with a smooth, transparent and integrated articular surface. Moreover, histological analysis showed obvious differences in cartilage regeneration. At week 4, the EPC-PLGA group showed considerably higher TGF-beta 2 and TGF-beta 3 expression, a greater amount of synthesized glycosaminoglycan (GAG) content, and a higher degree of osteochondral angiogenesis in repaired tissues. At week 12, the EPC-PLGA group showed enhanced hyaline cartilage regeneration with a normal columnar chondrocyte arrangement, higher SOX9 expression, and greater GAG and collagen type II (COLII) content. Moreover, the EPC-PLGA group showed organized osteochondral integration, the formation of vessel-rich tubercular bone and significantly higher bone volume per tissue volume and trabecular thickness (Tb.Th).Conclusion: The present EPC-PLGA cell delivery system generates a suitable in situ microenvironment for osteochondral regeneration without the supplement of exogenous growth factors. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.