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Cartilage resurfacing potential of PLGA scaffolds loaded with autologous cells from cartilage fat and bone marrow in an ovine model of osteochondral focal defect

机译:在骨骼软骨局灶性缺损的绵羊模型中PLGA支架的软骨重铺潜力充满了软骨脂肪和骨髓的自体细胞

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摘要

Current developments in tissue engineering strategies for articular cartilage regeneration focus on the design of supportive three-dimensional scaffolds and their use in combination with cells from different sources. The challenge of translating initial successes in small laboratory animals into the clinics involves pilot studies in large animal models, where safety and efficacy should be investigated during prolonged follow-up periods. Here we present, in a single study, the long-term (up to 1 year) effect of biocompatible porous scaffolds non-seeded and seeded with fresh ex vivo expanded autologous progenitor cells that were derived from three different cell sources [cartilage, fat and bone marrow (BM)] in order to evaluate their advantages as cartilage resurfacing agents. An ovine model of critical size osteochondral focal defect was used and the test items were implanted arthroscopically into the knees. Evidence of regeneration of hyaline quality tissue was observed at 6 and 12 months post-treatment with variable success depending on the cell source. Cartilage and BM-derived mesenchymal stromal cells (MSC), but not those derived from fat, resulted in the best quality of new cartilage, as judged qualitatively by magnetic resonance imaging and macroscopic assessment, and by histological quantitative scores. Given the limitations in sourcing cartilage tissue and the risk of donor site morbidity, BM emerges as a preferential source of MSC for novel cartilage resurfacing therapies of osteochondral defects using copolymeric poly-d,l-lactide-co-glycolide scaffolds. Electronic supplementary materialThe online version of this article (doi:10.1007/s10616-015-9842-4) contains supplementary material, which is available to authorized users.
机译:用于关节软骨再生的组织工程策略的当前发展集中于支持性三维支架的设计及其与不同来源的细胞结合使用。将小型实验动物的初步成功转化为临床的挑战涉及大型动物模型的试点研究,在这种情况下,应在延长的随访期内研究安全性和有效性。在这里,我们在一项研究中介绍了非播种并接种新鲜的离体扩增自体祖细胞的生物相容性多孔支架的长期(至一年)效应,所述祖细胞源自三种不同的细胞来源[软骨,脂肪和脂肪[BM(骨髓)(BM)],以评估其作为软骨表面置换剂的优势。使用了临界尺寸的骨软骨局灶性缺损的绵羊模型,并将测试物通过关节镜植入膝盖。在治疗后6和12个月观察到透明质组织再生的证据,根据细胞来源的不同,成功的程度也不同。软骨和BM来源的间充质基质细胞(MSC)而非脂肪来源的间充质基质细胞,通过磁共振成像和宏观评估以及组织学定量评分定性判断,可导致新软骨的最佳质量。考虑到软骨组织来源的局限性和供体部位发病的风险,BM成为使用共聚聚-d,l-丙交酯-乙交酯共聚支架的新型软骨修复骨软骨缺损的MSC的优先来源。电子补充材料本文的在线版本(doi:10.1007 / s10616-015-9842-4)包含补充材料,授权用户可以使用。

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