Cartilage fragments combined with BMSCs-Derived exosomes can promote tendon-bone healing after ACL reconstruction.
Cartilage fragments combined with BMSCs-Derived exosomes can promote tendon-bone healing after ACL reconstruction.
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DOI：
10.1016/j.mtbio.2023.100819
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发表时间：
2023-12
影响因子：
8.2
通讯作者：
Wang, Yue
中科院分区：
文献类型：
--
作者：
Zhang, Chi;Jiang, Chao;Jin, Jiale;Lei, Pengfei;Cai, Youzhi;Wang, Yue
前交叉韧带重建（ACLR）往往失败，因为肌腱-骨融合不能再生正常组织和纤维瘢痕组织的形成在肌腱-骨界面。来源于骨间充质间质细胞（BMSCs-Exos）的软骨碎片和外泌体可以促进内生体愈合。然而，ACLR对肌腱-骨愈合的影响尚不清楚。本研究发现BMSCs-Exos可以促进软骨碎片中软骨细胞的增殖，激活软骨相关基因SOX9和Aggrecan的表达。最佳效果浓度为1012个事件/uL。此外，BMSCs-Exos可以显著上调软骨碎片中BMP7和Smad5的表达，进一步增强软骨形成基因的表达。此外，本研究建立大鼠ACLR模型，将BMSCs-Exos/软骨碎片复合物植入股骨隧道。结果显示，术后8周，BE-CF组股骨隧道的平均直径明显小于CF组（p = 0.038）和对照组（p = 0.007）。此外，BE-CF组在股骨隧道中观察到更多的新骨形成，重建CT扫描显示BV/TV比更大。组织学结果还显示肌腱-骨结构再生，特别是纤维软骨。因此，这些发现提供了一个有希望的结果，BMSCs-Exos/软骨碎片复合物可以防止ACLR后骨隧道扩大并促进肌腱-骨愈合，这可能是由于BMP7/Smad5信号轴的调节。
Anterior cruciate ligament reconstruction (ACLR) often fails due to the inability of tendon-bone integration to regenerate normal tissues and formation of fibrous scar tissues in the tendon-bone interface. Cartilage fragments and exosomes derived from bone mesenchymal stromal cells (BMSCs-Exos) can enhance enthesis healing. Nevertheless, the effects on the tendon-bone healing of ACLR remain unknown. This study found that BMSCs-Exos can promote the proliferation of chondrocytes in cartilage fragments, and activated the expression of chondro-related genes SOX9 and Aggrecan. The optimal effect concentration was 1012 events/uL. Besides, BMSCs-Exos could significantly upregulated the expression of BMP7 and Smad5 in cartilage fragments, and further enhanced the expression of chondrogenic genes. Moreover, this study established a rat model of ACLR and implanted the BMSCs-Exos/cartilage fragment complex into the femoral bone tunnel. Results demonstrated that the mean diameters of the femoral bone tunnels were significantly smaller in the BE-CF group than those in the CF group (p = 0.038) and control group (p = 0.007) at 8 weeks after surgery. Besides, more new bone formation was observed in the femoral tunnels in the BE-CF group, as demonstrated by a larger BV/TV ratio based on the reconstructed CT scans. Histological results also revealed the regeneration of tendon-bone structures, especially fibrocartilage. Thus, these findings provide a promising result that BMSCs-Exos/cartilage fragment complex can prevent the enlargement of bone tunnel and promote tendon-bone healing after ACLR, which may have resulted from the regulation of the BMP7/Smad5 signaling axis.
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7.5
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