One-Step Surgical Procedure for the Treatment of Osteochondral Defects with Adipose-Derived Stem Cells in a Caprine Knee Defect: A Pilot Study

One-Step Surgical Procedure for the Treatment of Osteochondral Defects with Adipose-Derived Stem Cells in a Caprine Knee Defect: A Pilot Study
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DOI:
10.1089/biores.2013.0024
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发表时间:
2013-08-01
影响因子:
--
通讯作者:
Helder, Marco N.
Helder, Marco N.
中科院分区:
其他
文献类型:
--
作者:
Jurgens, Wouter J. F. M.;Kroeze, Robert Jan;Helder, Marco N.

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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。脂肪源性基质血管成分(SVF)细胞因其丰富的可用性和高频率而允许一步手术程序的发展。在这项初步研究中,我们评估了这种概念的体内安全性,可行性和有效性,使用新鲜分离的(SVF)或培养的脂肪干细胞(ASC)接种支架,并将其与无细胞对应物进行比较。在8只山羊的膝关节内侧髁和滑车沟内造成骨软骨缺损。缺损用无细胞胶原I/III支架或接种SVF细胞或培养的ASC的支架填充。1个月和4个月后通过肉眼观察、免疫组织化学、生物力学分析、microCT分析和生物化学评价骨软骨再生。1个月后,未观察到不良反应。显微镜而非宏观评价显示出相当大但不显著的差异,其中细胞加载的构建体显示出更广泛的再生。4个月后,无细胞构建体显示出增加的再生,然而,在较低程度上比细胞处理的构建体。后者表现出更广泛的II型胶原蛋白,透明样软骨,和更高的弹性模量,和软骨层中的糖胺聚糖含量更好地接近天然组织值。此外,它们的缺损区域含有更高水平的再生、成熟的软骨下骨,具有更强烈的I型胶原染色。SVF细胞倾向于在所有参数上表现最好。总之,该初步研究证明了骨软骨缺损再生一步手术的临床前安全性和可行性。在新鲜分离的SVF细胞和培养的ASCs之间发现类似的再生。需要更大规模的研究和更长时间的随访来证实这些发现。
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.