Reconstruction of cartilage with clonal mesenchymal stem cell-acellular dermal matrix in cartilage defect model in nonhuman primates
Reconstruction of cartilage with clonal mesenchymal stem cell-acellular dermal matrix in cartilage defect model in nonhuman primates
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DOI：
10.1016/j.intimp.2013.02.005
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发表时间：
2013-07-01
影响因子：
5.6
通讯作者：
Chen, Huifang
中科院分区：
文献类型：
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作者：
Ma, Anlun;Jiang, Li;Chen, Huifang
目的：关节软骨缺陷通常与创伤、炎症和骨关节炎有关。基于间充质干细胞（MSC）的疗法是一种有前途的修复关节软骨的新方法。直接关节内注射未定型的间充质干细胞并不能再生高质量的软骨。本研究探索利用新型三维、选择性软骨形成克隆 MSC 负载猴脱细胞真皮基质 (MSC-ADM) 支架来修复食蟹猴膝关节软骨缺损实验模型中受损的软骨。方法：对 MSC 的细胞大小、细胞产量、表型、增殖和软骨形成分化能力进行表征。通过硫酸化糖胺聚糖 (sGAG)、胶原蛋白和荧光激活细胞分选仪 (FACS) 分析，在不同的 MSC 传代中进行软骨形成分化测定。将选定的软骨形成克隆 MSC 接种到具有夹心模型的 ADM 支架上，并通过共焦显微镜和扫描电子显微镜对装载 MSC 的 ADM 移植物进行分析。分别用生理盐水、克隆MSC和克隆MSC-ADM移植物治疗软骨缺损。分别在治疗后第8、16、24周评估临床参数、组织学和免疫组化检查。结果：多克隆和克隆MSC在合适的成软骨因子刺激后可以分化成成软骨谱系。它们表达间充质标记物，但造血标记物呈阴性。通过选择基于 MSC 的软骨形成克隆治疗，关节软骨缺陷得到显着改善和修复，特别是在 MSC-ADM 治疗组中。 MSC-ADM治疗组的组织学评分始终高于其他组。结论：我们的结果表明，选定的软骨形成克隆MSC负载ADM移植物可以改善食蟹猴模型中的软骨损伤，这可能适用于修复类似的人类软骨缺损。 (C) 2013 Elsevier B.V. 保留所有权利。
Objective: Articular cartilage defects are commonly associated with trauma, inflammation and osteoarthritis. Mesenchymal stem cell (MSC)-based therapy is a promising novel approach for repairing articular cartilage. Direct intra-articular injection of uncommitted MSCs does not regenerate high-quality cartilage. This study explored utilization of a new three-dimensional, selected chondrogenic clonal MSC-loaded monkey acellular dermal matrix (MSC-ADM) scaffold to repair damaged cartilage in an experimental model of knee joint cartilage defect in Cynomolgus monkeys.Methods: MSCs were characterized for cell size, cell yield, phenotypes, proliferation and chondrogenic differentiation capacity. Chondrogenic differentiation assays were performed at different MSC passages by sulfated glycosaminoglycans (sGAG), collagen, and fluorescence activated cell sorter (FACS) analysis. Selected chondrogenic clonal MSCs were seeded onto ADM scaffold with the sandwich model and MSC-loaded ADM grafts were analyzed by confocal microscopy and scanning electron microscopy. Cartilage defects were treated with normal saline, clonal MSCs and clonal MSC-ADM grafts, respectively. The clinical parameters, and histological and immunohistochemical examinations were evaluated at weeks 8, 16, 24 post-treatment, respectively.Results: Polyclonal and clonal MSCs could differentiate into the chondrogenic lineage after stimulation with suitable chondrogenic factors. They expressed mesenchymal markers and were negative for hematopoietic markers. Articular cartilage defects were considerably improved and repaired by selected chondrogenic clonal MSC-based treatment, particularly, in MSC-ADM-treated group. The histological scores in MSC-ADM-treated group were consistently higher than those of other groups.Conclusion: Our results suggest that selected chondrogenic clonal MSC-loaded ADM grafts could improve the cartilage lesions in Cynomolgus monkey model, which may be applicable for repairing similar human cartilage defects. (C) 2013 Elsevier B.V. All rights reserved.