Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon–bone healing

Abstract

Tendon–bone insertion (TBI) injuries, such as anterior cruciate ligament injury and rotator cuff injury, are the most common soft tissue injuries. In most situations, surgical tendon/ligament reconstruction is necessary for treating such injuries. However, a significant number of cases failed because healing of the enthesis occurs through scar tissue formation rather than the regeneration of transitional tissue. In recent years, the therapeutic potential of mesenchymal stem cells (MSCs) has been well documented in animal and clinical studies, such as chronic paraplegia, non-ischemic heart failure, and osteoarthritis of the knee. MSCs are multipotent stem cells, which have self-renewability and the ability to differentiate into a wide variety of cells such as chondrocytes, osteoblasts, and adipocytes. Numerous studies have suggested that MSCs could promote angiogenesis and cell proliferation, reduce inflammation, and produce a large number of bioactive molecules involved in the repair. These effects are likely mediated by the paracrine mechanisms of MSCs, particularly through the release of exosomes. Exosomes, nano-sized extracellular vesicles (EVs) with a lipid bilayer and a membrane structure, are naturally released by various cell types. They play an essential role in intercellular communication by transferring bioactive lipids, proteins, and nucleic acids, such as mRNAs and miRNAs, between cells to influence the physiological and pathological processes of recipient cells. Exosomes have been shown to facilitate tissue repair and regeneration. Herein, we discuss the prospective applications of MSC-derived exosomes in TBI injuries. We also review the roles of MSC–EVs and the underlying mechanisms of their effects on promoting tendon–bone healing. At last, we discuss the present challenges and future research directions. Graphical Abstract

Aging‐Related Rotator Cuff Tears: Molecular Mechanisms and Implications for Clinical Management

“…Emerging evidence has indicated the potential of mesenchymal stem cells (MSCs) in mitigating degenerative changes associated with RCT, thereby improving surgical repair outcomes. [76][77][78] This potential can be attributed to their ability for multilineage differentiation. Nonetheless, it is noteworthy that the regenerative capacity of MSCs may be compromised with aging, limiting their effectiveness in addressing aging-related muscle degeneration.…”

Engineered exosomes for tissue regeneration: from biouptake, functionalization and biosafety to applications

“…They are mainly involved in regulation through the indirect pathway of paracrine secretion to promote tissue regeneration. 173 Exosomes from Mesenchymal Stem Cells (MSC-Exo) reduce inflammation, promote proliferation, inhibit apoptosis, and promote angiogenesis during tissue healing processes. 174 Macrophages are heterogeneous cells that can polarize into different phenotypes in different micro-environments.…”

Nanofibrous scaffolds for the healing of the fibrocartilaginous enthesis: advances and prospects

“…12,13 Surgical repair and reconstruction typically only restore the anatomical structure of the fibrocartilaginous enthesis, and the scar tissue formed after healing lacks natural gradient structure and collagen fiber arrangement, resulting in poor mechanical properties that do not promote fibrocartilaginous enthesis regeneration. 14,15 In addition, some non-surgical therapies also have limitations. As is known, the natural healing process of the injury is complex, including inflammation, rapid proliferation, and gradual remodeling.…”