The effect of adipose-derived stem cell sheets and CTGF on early flexor tendon healing in a canine model
The effect of adipose-derived stem cell sheets and CTGF on early flexor tendon healing in a canine model
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DOI：
10.1038/s41598-018-29474-8
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发表时间：
2018-07-23
影响因子：
4.6
通讯作者：
Thomopoulos, Stavros
中科院分区：
文献类型：
--
作者：
Shen, Hua;Jayaram, Rohith;Thomopoulos, Stavros
滑膜内肌腱损伤是骨科中最具挑战性的。尽管手术和康复方法有了显著的改进，但功能结局仍然受到粘连、间隙形成和破裂的限制。粘连由过度炎症引起，而肌腱间隙和断裂由炎症诱导的基质降解和再生不足引起。因此，本研究使用了一种联合治疗方法，用脂肪来源的间充质基质细胞（ASC）调节炎症，同时用结缔组织生长因子（CTGF）刺激肌腱再生。通过细胞片将ASC应用于修复表面，并通过多孔缝线将CTGF递送至修复中心。在犬屈肌腱损伤模型中，在修复后14天评估联合治疗的效果。CTGF单独或与ASC一起，与对照修复相比，减少炎症（IL 1B和IL 6）和基质降解（MMP 3和MMP 13）基因表达，同时增加抗炎基因（IL 4）表达和胶原蛋白合成。联合治疗比单独CTGF治疗更有效，减少了炎性IFNG和瘢痕相关的COL 3A 1基因表达，增加了肌腱表面和沿着核心缝合线内部的CD 146（+）肌腱干/祖细胞。因此，该联合入路在促进屈肌腱早期愈合方面具有良好的应用前景，值得进一步研究。
Intrasynovial tendon injuries are among the most challenging in orthopedics. Despite significant improvements in operative and rehabilitation methods, functional outcomes continue to be limited by adhesions, gap formation, and rupture. Adhesions result from excessive inflammation, whereas tendon gapping and rupture result from inflammation-induced matrix degradation and insufficient regeneration. Therefore, this study used a combined treatment approach to modulate inflammation with adipose-derived mesenchymal stromal cells (ASCs) while stimulating tendon regeneration with connective tissue growth factor (CTGF). ASCs were applied to the repair surface via cell sheets and CTGF was delivered to the repair center via porous sutures. The effect of the combined treatment was assessed fourteen days after repair in a canine flexor tendon injury model. CTGF, either alone or with ASCs, reduced inflammatory (IL1B and IL6) and matrix degrading (MMP3 and MMP13) gene expression, while increasing anti-inflammatory gene (IL4) expression and collagen synthesis compared to control repairs. The combined treatment was more effective than CTGF treatment alone, reducing the inflammatory IFNG and scar-associated COL3A1 gene expression and increasing CD146(+) tendon stem/progenitor cells at the tendon surface and interior along the core suture tracks. Therefore, the combined approach is promising in promoting early flexor tendon healing and worthy of further investigation.