Effect of self-assembling peptide, chondrogenic factors, and bone marrow-derived stromal cells on osteochondral repair.

Effect of self-assembling peptide, chondrogenic factors, and bone marrow-derived stromal cells on osteochondral repair.
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DOI:
10.1016/j.joca.2010.09.004
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发表时间:
2010-12
影响因子:
7
通讯作者:
Frisbie, D. D.
Frisbie, D. D.
中科院分区:
医学2区
文献类型:
--
作者:
Miller, R. E.;Grodzinsky, A. J.;Vanderploeg, E. J.;Lee, C.;Ferris, D. J.;Barrett, M. F.;Kisiday, J. D.;Frisbie, D. D.

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本研究的目的是测试可注射自组装肽(KLD)水凝胶与或不与软骨形成因子(CF)和同种异体骨髓基质细胞(BMSC)刺激软骨再生的能力在全厚度,临界尺寸,兔软骨缺损模型在体内。我们使用CF处理来测试CF将通过迁移到无细胞KLD(KLD+CF)中的细胞或通过在KLD中递送的BMSC(KLD+CF+ BMSC)刺激软骨形成和基质产生的假设。针对对侧未处理对照测试三组:KLD、KLD+CF和KLD+CF+ BMSC,n=6-7。将TGF-β1、地塞米松和IGF-1作为软骨形成因子(CF)与KLD和BMSCs在注射前预混合。评价包括大体、组织学、免疫组织化学和放射学分析。无CF或BMSC的KLD在12周后表现出最大的修复,其番红-O、胶原II免疫染色和累积组织学评分显著高于未治疗的对侧对照。KLD+CF导致比未处理的对侧对照显著更高的聚集蛋白聚糖免疫染色。与单独使用KLD相比,包括同种异体BMSC +CF显着降低了修复质量并增加了骨赘形成。这些数据表明,KLD可以原位填充全层骨软骨缺损,并改善软骨修复,如番红-O、胶原II免疫染色和累积组织学所示。在这个小动物模型中,全层临界尺寸的缺损提供了进入骨髓的途径,在概念上类似于大型动物模型中的磨损关节成形术或海绵化,并表明将KLD与这些技术相结合可能会改善当前的实践。
The goal of this study was to test the ability of an injectable self-assembling peptide (KLD) hydrogel with or without chondrogenic factors (CF) and allogeneic bone marrow stromal cells (BMSCs) to stimulate cartilage regeneration in a full-thickness, critically-sized, rabbit cartilage defect model in vivo. We used CF treatments to test the hypotheses that CF would stimulate chondrogenesis and matrix production by cells migrating into acellular KLD (KLD+CF) or by BMSCs delivered in KLD (KLD+CF+BMSCs). Three groups were tested against contralateral untreated controls: KLD, KLD+CF, and KLD+CF+BMSCs, n=6–7. TGF-β1, dexamethasone, and IGF-1 were used as chondrogenic factors (CF) pre-mixed with KLD and BMSCs before injection. Evaluations included gross, histological, immunohistochemical and radiographic analyses. KLD without CF or BMSCs showed the greatest repair after 12 weeks with significantly higher Safranin-O, collagen II immunostaining, and cumulative histology scores than untreated contralateral controls. KLD+CF resulted in significantly higher aggrecan immunostaining than untreated contralateral controls. Including allogeneic BMSCs+CF markedly reduced the quality of repair and increased osteophyte formation compared to KLD alone. These data show that KLD can fill full-thickness osteochondral defects in situ and improve cartilage repair as shown by Safranin-O, collagen II immunostaining, and cumulative histology. In this small animal model, the full-thickness critically-sized defect provided access to the marrow, similar in concept to abrasion arthroplasty or spongialization in large animal models, and suggests that combining KLD with these techniques may improve current practice.
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