Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites
Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites
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DOI：
10.1002/jor.1100170404
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发表时间：
1999-07-01
影响因子：
2.8
通讯作者：
Mohammed, H
中科院分区：
文献类型：
--
作者：
Nixon, AJ;Fortier, LA;Mohammed, H
在急性损伤中，骨床松质间隙固有的干细胞为软骨修复提供了多能细胞的重要来源。胰岛素样生长因子-I促进骨髓源性干细胞在长期培养中的软骨形成，并可能在体内愈合软骨病变中增强软骨形成。本研究探讨了胰岛素样生长因子-I的影响，逐渐释放的纤维蛋白凝块聚合在原位，对可招募的干细胞池在全层临界软骨缺损模型。12个全厚15毫米的软骨病变的股髌关节的6个年轻的成熟的马进行了修复注射的自体纤维蛋白含有25微克的人重组胰岛素样生长因子-I或，在控制关节，纤维蛋白没有生长因子。所有马在6个月时处死，通过组织学、组织化学、I型和II型胶原免疫组织化学、I型和II型胶原原位杂交和基质生化测定评估软骨修复组织和周围软骨。白色组织填充移植物和对照病变，生长因子处理的缺损更完全填充并牢固地附着于软骨下骨。生长因子治疗缺损的组织学评价显示，软骨细胞群中度改善，柱状细胞组织更多，与下层骨的附着更好。II型前胶原mRNA是丰富的存在于较深的一半的治疗部分相比，在控制组织中的中度信息表达。II型胶原蛋白的免疫定位显示生长因子治疗的病变中胶原蛋白占优势，证实II型信息翻译为蛋白质。治疗后缺损的复合组织学愈合评分比对照缺损显著改善。治疗组和对照组关节软骨缺损处的DNA含量相似。基质蛋白多糖含量在治疗和对照缺损中相似，并且在缺损中低于治疗和对照关节的完整周围和远端软骨。II型胶原的比例显着增加，在生长因子治疗的组织。富含胰岛素样生长因子-I的纤维素聚合物改善了组织学外观和II型胶原在愈合的全层软骨病变中的比例。然而，没有一个生化或形态学特征与正常关节软骨一致。
Stem cells indigenous to the cancellous spaces of the bone bed in an acute injury provide an important source of pluripotent cells for cartilage repair. Insulin-like growth factor-I facilitates chondrogenesis of bone marrow-derived stem cells in long-term culture and may enhance chondrogenesis in healing cartilage lesions in vivo. This study examined the impact of insulin-like growth factor-I, gradually released from fibrin clots polymerized in situ, on the recruitable stem-cell pool in a full-thickness critical cartilage defect model. Twelve full-thickness 15-mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by an injection of autogenous fibrin containing 25 mu g of human recombinant insulin-like growth factor-I or, in control joints, fibrin without the growth factor. All horses were killed at 6 months, and cartilage repair tissue and surrounding cartilage were assessed by histology, histochemistry, types I and II collagen immunohistochemistry, types I and II collagen in situ hybridization, and matrix biochemical determinations. White tissue filled grafted and control lesions, with the growth factor-treated defects being more completely filled and securely attached to the subchondral bone. A moderately improved chondrocyte population, more columnar cellular organization, and better attachment to the underlying bone were evident on histological evaluation of growth factor-treated defects. Type-II procollagen mRNA was abundantly present in the deeper half of the treated sections compared with moderate message expression in control tissues. Immunolocalization of type-II collagen showed a preponderance of the collagen in growth factor-treated lesions, confirming translation of type-II message to protein. Composite histologic healing scores for treated defects were significantly improved over those for control defects. DNA content in the cartilage defects was similar in treated and control joints. Matrix proteoglycan content was similar in treated and control defects and lower in the defects than in the intact surrounding and re:mote cartilage of the treated and control joints. The proportion of type-II collagen significantly increased in growth factor-treated tissues. Fibrin polymers laden with insulin-like growth factor-I improved the histologic appearance and the proportion of type-II collagen in healing, full-thickness cartilage lesions. However, none of the biochemical or morphologic features were consistent with those of normal articular cartilage.