Age-different BMSCs-derived exosomes accelerate tendon-bone interface healing in rotator cuff tears model.

Area of Science:

• Orthopedics
• Regenerative Medicine
• Biotechnology

Background:

• Rotator cuff tears (RCTs) are a common cause of shoulder pain and dysfunction.
• Improper healing at the tendon-bone interface (TBI) frequently leads to retears after RCTs.
• Investigating novel therapeutic strategies for TBI healing is crucial.

Purpose of the Study:

• To investigate the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes in promoting TBI healing after RCTs.
• To compare the efficacy of exosomes derived from young BMSCs (Y-BMSCs-exo) versus aged BMSCs (A-BMSCs-exo).

Main Methods:

• RCTs models were established in rats, and exosomes from young and aged BMSCs were administered via hydrogel.
• Histological analysis (HE, Sirius Red, Oil Red O staining) was performed to evaluate TBI structure and composition.
• Western blotting and RT-qPCR were used to assess key protein and mRNA expression related to extracellular matrix, tendon cells, osteogenesis, stemness, and angiogenesis.

Main Results:

• Both Y-BMSCs-exo and A-BMSCs-exo promoted organized collagen fiber growth and restored the typical fibrocartilage structure at the TBI.
• Exosome treatment significantly upregulated crucial genes and proteins involved in ECM deposition, osteogenesis, and angiogenesis.
• In vitro studies demonstrated that exosomes enhanced tendon cell and tendon-derived stem cell (TDSC) activity and stemness while reducing their osteogenic potential.
• Y-BMSCs-exo exhibited significantly greater therapeutic effects than A-BMSCs-exo.

Conclusions:

• BMSCs-derived exosomes effectively promote TBI healing in RCTs by facilitating ECM remodeling, osteogenic differentiation, and angiogenesis.
• These exosomes enhance the stemness of TDSCs, contributing to improved tissue regeneration.
• Utilizing exosomes from young BMSCs offers superior therapeutic outcomes for rotator cuff repair.