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骨髓间充质干细胞在肩袖修复模型中的应用。

Application of bone marrow-derived mesenchymal stem cells in a rotator cuff repair model.

机构信息

Hospital for Special Surgery, New York, NY 10021, USA.

出版信息

Am J Sports Med. 2009 Nov;37(11):2126-33. doi: 10.1177/0363546509339582. Epub 2009 Aug 14.

DOI:10.1177/0363546509339582
PMID:19684297
Abstract

BACKGROUND

Rotator cuff tendons heal to bone with interposed scar tissue, which makes repairs prone to failure. The purpose of this study was to determine if the application of bone marrow-derived mesenchymal stem cells (MSCs) can improve rotator cuff healing after repair.

HYPOTHESIS

Application of MSCs to the repair site will result in superior results compared with controls on histologic and biomechanical testing.

STUDY DESIGN

Controlled laboratory study.

METHODS

Ninety-eight Lewis rats underwent unilateral detachment and repair of the supraspinatus tendon; 10 rats were used for MSC harvest. Eight animals were used for cell tracking with Ad-LacZ. The remaining animals received either 10(6) MSCs in a fibrin carrier, the carrier alone, or nothing at the repair site. Animals were sacrificed at 2 and 4 weeks for histologic analysis to determine the amount of fibrocartilage formation and the collagen organization at the insertion. Biomechanical testing was also performed.

RESULTS

Specimens treated with Ad-LacZ-transduced MSCs exhibited more beta-galactosidase activity at the repair site compared with controls at both 2 and 4 weeks, although activity at 4 weeks was less than that at 2 weeks. There were no differences in the amount of new cartilage formation or collagen fiber organization between groups at either time point. There were also no differences in the biomechanical strength of the repairs, the cross-sectional area, peak stress to failure, or stiffness.

CONCLUSION

The addition of MSCs to the healing rotator cuff insertion site did not improve the structure, composition, or strength of the healing tendon attachment site despite evidence that they are present and metabolically active.

CLINICAL RELEVANCE

A biologic solution to the problem of tendon-to-bone healing in the rotator cuff remains elusive. The repair site may lack the cellular and/or molecular signals necessary to induce appropriate differentiation of transplanted cells. Further studies are needed to determine if cell-based strategies need to be combined with growth and differentiation factors to be effective.

摘要

背景

肩袖肌腱与骨之间愈合时有中间的瘢痕组织,这使得修复容易失败。本研究旨在确定骨髓间充质干细胞(MSCs)的应用是否可以改善肩袖修复后的愈合。

假设

将 MSCs 应用于修复部位,与对照组相比,在组织学和生物力学测试中会有更好的结果。

研究设计

对照的实验室研究。

方法

98 只 Lewis 大鼠进行了单侧冈上肌腱的分离和修复;10 只大鼠用于 MSC 收获。8 只动物用于 Ad-LacZ 细胞追踪。其余动物在修复部位接受纤维蛋白载体中的 10(6)MSCs、载体单独或不接受任何治疗。2 周和 4 周时处死动物进行组织学分析,以确定插入处纤维软骨形成和胶原组织的数量。还进行了生物力学测试。

结果

与对照组相比,转染 Ad-LacZ 的 MSC 处理的标本在 2 周和 4 周时在修复部位均表现出更多的β-半乳糖苷酶活性,尽管 4 周时的活性低于 2 周时的活性。在任何时间点,各组之间的新软骨形成量或胶原纤维组织均无差异。修复的生物力学强度、横截面积、破坏峰值应力或刚度也无差异。

结论

尽管有证据表明它们存在且代谢活跃,但将 MSCs 添加到愈合的肩袖插入部位并未改善愈合肌腱附着部位的结构、组成或强度。

临床相关性

解决肩袖中肌腱与骨骼愈合问题的生物解决方案仍然难以捉摸。修复部位可能缺乏诱导移植细胞适当分化所需的细胞和/或分子信号。需要进一步的研究来确定细胞为基础的策略是否需要与生长和分化因子结合才能有效。

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