Bone marrow mesenchymal stem cell-derived exosomes promote rotator cuff tendon-bone healing by promoting angiogenesis and regulating M1 macrophages in rats

Abstract

Background: Rotator cuff tears (RCTs) often require reconstructive surgery. Tendon-bone healing is critical for the outcome of rotator cuff reconstruction, but the process of tendon-bone healing is complex and difficult. Mesenchymal stem cells (MSCs) are considered to be an effective method to promote tendon-bone healing. MSCs have strong paracrine, anti-inflammatory, immunoregulatory, and angiogenic potential. Recent studies have shown that MSCs achieve many regulatory functions through exosomes. The purpose of this study was to explore the role of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) in tendon-bone healing. Methods: Our study found that BMSC-Exos promote the proliferation, migration, and angiogenic tube formation of Human Umbilical Vein Endothelial Cells (HUVECs). The mechanism by which BMSC-Exos achieve this may be through the regulation of the angiogenic signaling pathway. In addition, BMSC-Exos can inhibit the polarization of M1 macrophages and inhibit the secretion of proinflammatory factors by M1 macrophages. After rotator cuff reconstruction in rats, BMSC-Exos were injected into the tail vein to analyze their effect on the rotator cuff tendon-bone interface healing. Results: It was confirmed that BMSC-Exos increased the breaking load and stiffness of the rotator cuff after reconstruction in rats, induced angiogenesis around the rotator cuff endpoint, and promoted growth of the tendon-bone interface. Conclusion: BMSC-Exos promote tendon-bone healing after rotator cuff reconstruction in rats by promoting angiogenesis and inhibiting inflammation.

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“…These ndings suggested the possibility of a positive feedback loop, wherein osteoblastic-like cells secrete EGFL6 and EGFL6 promotes BMSCs differentiation. A mesenchymal stem cell (MSC) population resides in the perivascular niche of the bone marrow [56,57]. Other than their capacity to transdifferentiate or differentiate into osteoblasts, BMSCs themselves can communicate with ECs and integrate into the bone regeneration framework [58,59].…”

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“…This may be due to the synergistic effect of BMSC. BMSC have autocrine and paracrine functions, and can secrete many soluble growth factors and cytokines, as well as exosomes, which can bene t to EPC proliferation, migration and formation of blood vessels [44,45].…”