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层粘连蛋白凝胶中 IGF-1 和 TGF-β1 联合骨髓间充质干细胞修复兔膝关节骨软骨缺损。

Mesenchymal stem cells with IGF-1 and TGF- β1 in laminin gel for osteochondral defects in rabbits.

机构信息

Division of Surgery, Indian Veterinary Research Institute (IVRI), Izatnagar, India; Clinical Veterinary Services Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, SKUAST-K, India.

Division of Surgery, Indian Veterinary Research Institute (IVRI), Izatnagar, India.

出版信息

Biomed Pharmacother. 2017 Sep;93:1165-1174. doi: 10.1016/j.biopha.2017.07.032. Epub 2017 Jul 19.

Abstract

OBJECTIVE

Healing of articular cartilage is still a challenge due to its limited potential to regenerate. In the present study, we evaluated allogenic bone marrow mesenchymal stem cells (BM-MSCs) alone or in combination with growth factors, insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1) in laminin scaffolds for healing of osteochondral defects.

DESIGN

Osteochondral defects of 4mm (diameter) x 5mm (depth) were induced in the rabbit knee joints and treated with phosphate-buffered saline (PBS; control), BM-MSCs, BM-MSCs in laminin, BM-MSCs in laminin with IGF-1, or BM-MSCs in laminin with IGF-1 and TGF-β1 in 10 animals each. Gross, radiographic, scanning electron microscopic (SEM) and histologic examinations besides chondrocyte-specific genes expression by quantitative real time qPCR were carried out at 8 and 12 weeks.

RESULTS

Gross and SEM examination revealed superior morphology and surface architecture of the healing site in animals that received MSCs with IGF-1 or IGF-1 and TGF-β1. The application of laminin composites containing MSCs with IGF-1 and TGF-β1 significantly enhanced hyaline cartilage formation with improved cellular arrangement, proteoglycan deposition, clear tidemark zone and subchondral bone formation. However, regenerated tissue in defects that received only MSCs had poor tidemark zone and proteoglycans deposition Aggrecan and Coll2 expression was significantly higher in case of MSCs with growth factors.

CONCLUSION

The treatment with BM-MSCs combined with IGF-1/TGF-β1 into laminin gel scaffold might enhance the restoration of hyaline cartilage in osteochondral defect.

摘要

目的

由于关节软骨再生能力有限,因此其愈合仍然是一个挑战。在本研究中,我们评估了同种异体骨髓间充质干细胞(BM-MSCs)单独或与生长因子胰岛素样生长因子-1(IGF-1)和转化生长因子-β1(TGF-β1)联合在层粘连蛋白支架中用于骨软骨缺损愈合的情况。

设计

在 10 只兔膝关节中诱导 4mm(直径)x 5mm(深度)的骨软骨缺损,并分别用磷酸盐缓冲盐水(PBS;对照组)、BM-MSCs、层粘连蛋白中的 BM-MSCs、含 IGF-1 的层粘连蛋白中的 BM-MSCs 以及含 IGF-1 和 TGF-β1 的层粘连蛋白中的 BM-MSCs 进行治疗。在 8 周和 12 周时进行大体、放射学、扫描电子显微镜(SEM)和组织学检查,以及通过定量实时 qPCR 检测软骨细胞特异性基因的表达。

结果

大体和 SEM 检查显示,接受含 IGF-1 或 IGF-1 和 TGF-β1 的 MSC 的动物的愈合部位具有更好的形态和表面结构。应用含有 IGF-1 和 TGF-β1 的 MSC 的层粘连蛋白复合材料显著增强了透明软骨的形成,改善了细胞排列、糖胺聚糖沉积、清晰的边界带和软骨下骨形成。然而,仅接受 MSC 治疗的缺陷部位的再生组织边界带和糖胺聚糖沉积较差。在有生长因子的 MSC 情况下,聚集蛋白和 Coll2 的表达明显更高。

结论

将 BM-MSCs 与 IGF-1/TGF-β1 联合应用于层粘连蛋白凝胶支架中可能会增强骨软骨缺损中透明软骨的修复。

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