Jurgens Wouter J F M, Kroeze Robert Jan, Zandieh-Doulabi Behrouz, van Dijk Annemieke, Renders Greetje A P, Smit Theo H, van Milligen Florine J, Ritt Marco J P F, Helder Marco N
Department of Plastic, Reconstructive, & Hand Surgery, VU University Medical Center (VUmc), Amsterdam, The Netherlands . ; MOVE/Skeletal Tissue Engineering Group Amsterdam (STEGA) , Amsterdam, The Netherlands .
Biores Open Access. 2013 Aug;2(4):315-25. doi: 10.1089/biores.2013.0024.
Regenerative therapies offer attractive alternatives for the treatment of osteochondral defects. Adipose-derived stromal vascular fraction (SVF) cells allow the development of one-step surgical procedures by their abundant availability and high frequency. In this pilot study we evaluated the in vivo safety, feasibility, and efficacy of this concept using scaffolds seeded with freshly isolated (SVF) or cultured adipose stem cells (ASCs), and compared these to their acellular counterparts. Osteochondral defects were created in medial condyles and trochlear grooves in knees of eight goats. Defects were filled with acellular collagen I/III scaffolds or scaffolds seeded with SVF cells or cultured ASCs. Osteochondral regeneration was evaluated after 1 and 4 months by macroscopy, immunohistochemistry, biomechanical analysis, microCT analysis, and biochemistry. After 1 month, no adverse effects were noted. Microscopic, but not macroscopic evaluation showed considerable yet not significant differences, with cell-loaded constructs showing more extensive regeneration. After 4 months, acellular constructs displayed increased regeneration, however, to a lesser degree than cell-treated constructs. The latter exhibited more extensive collagen type II, hyaline-like cartilage, and higher elastic moduli, and their glycosaminoglycan content in the cartilaginous layer better approached native tissue values. Moreover, their defect regions contained higher levels of regenerated, mature subchondral bone with more intense collagen type I staining. SVF cells tended to perform best on all parameters. In summary, this pilot study demonstrated the preclinical safety and feasibility of a one-step surgical procedure for osteochondral defect regeneration. Similar regeneration was found between freshly isolated SVF cells and cultured ASCs. Larger studies with longer follow-up are required to substantiate these findings.
再生疗法为骨软骨缺损的治疗提供了有吸引力的替代方案。脂肪来源的基质血管组分（SVF）细胞因其丰富的可获得性和高频率，使得一步式手术操作得以开展。在这项前瞻性研究中，我们使用接种了新鲜分离的（SVF）或培养的脂肪干细胞（ASC）的支架，评估了该概念在体内的安全性、可行性和有效性，并将其与无细胞对应物进行了比较。在八只山羊的膝关节内侧髁和滑车沟制造骨软骨缺损。缺损处填充无细胞I/III型胶原支架或接种了SVF细胞或培养的ASC的支架。在1个月和4个月后，通过大体观察、免疫组织化学、生物力学分析、显微CT分析和生物化学评估骨软骨再生情况。1个月后，未观察到不良反应。微观评估（而非宏观评估）显示出相当但不显著的差异，细胞负载构建体显示出更广泛的再生。4个月后，无细胞构建体的再生增加，然而，程度低于细胞处理构建体。后者表现出更广泛的II型胶原、透明样软骨，以及更高的弹性模量，并且其软骨层中的糖胺聚糖含量更接近天然组织值。此外，它们的缺损区域含有更高水平的再生成熟软骨下骨，I型胶原染色更强。在所有参数上，SVF细胞往往表现最佳。总之，这项前瞻性研究证明了骨软骨缺损再生一步式手术操作在临床前的安全性和可行性。在新鲜分离的SVF细胞和培养的ASC之间发现了类似的再生情况。需要进行更大规模、更长随访期的研究来证实这些发现。
