In Situ-Forming Fibrin Gel Encapsulation of MSC-Exosomes for Partial-Thickness Rotator Cuff Tears in a Rabbit Model

Abstract

Background:Current nonoperative treatments for partial-thickness rotator cuff tears (PTRCTs) have limited effectiveness in preventing tear progression or promoting tendon healing. This study aimed to establish a rabbit model using in situ-forming fibrin gel containing adipose stem cell-derived exosomes (ASC-Exos/fibrin) to treat PTRCTs.Methods:Fifty-six rabbits (112 shoulders) were included in this study and assigned to 4 groups: the control group (32 shoulders; PTRCTs without treatment), the fibrin group (32 shoulders; PTRCTs treated with fibrin gel), the ASC-Exo/fibrin group (32 shoulders; PTRCTs treated with ASC-Exos/fibrin), and the sham group (16 shoulders; sham surgery). Bilateral, 50%-thickness, bursal-side PTRCTs of 1 mm (depth) × 3 mm (width) × 5 mm (length) on the supraspinatus tendon were established by a number-11 scalpel blade, with accuracy of the measurement ensured by a digital vernier caliper. At 6 and 12 weeks postoperatively, gross observation, measurement of the thickness of residual supraspinatus tendons, and histological and biomechanical analyses were performed to analyze tendon repair.Results:At 12 weeks postoperatively, the tendon thickness in the ASC-Exos/fibrin group (mean and standard deviation, 1.63 ± 0.19 mm) was significantly greater than in the control group (0.85 ± 0.09 mm) (p < 0.0001) and fibrin group (1.16 ± 0.17 mm) (p < 0.0001). The histological score in the ASC-Exos/fibrin group (6.25 ± 0.53) was significantly better than in the control group (11.38 ± 0.72) (p < 0.0001) and fibrin group (9.00 ± 0.54) (p < 0.0001). Overall, immunohistochemical staining of types-I and III collagen and biomechanical testing also showed ASC-Exos/fibrin to be more effective in repairing PTRCTs than fibrin alone and no treatment.Conclusions:Local administration of in situ-forming ASC-Exos/fibrin effectively facilitated the healing of bursal-side PTRCTs in rabbits. This approach may be a candidate for the nonoperative management of PTRCTs.Clinical Relevance:Ultrasound-guided injection of ASC-Exos/fibrin may be a novel nonoperative strategy to treat PTRCTs.

NAMPT encapsulated by extracellular vesicles from young adipose-derived mesenchymal stem cells treated tendinopathy in a “One-Stone-Two-Birds” manner

“…The results of this study provide supportive data for ADMSC young -EVs in tendinopathy therapy and highlight their effects on both tenocytes and macrophages. Two previous studies on ADMSC-derived EVs in tendon repair did not provide the age of donors [ 31 , 32 ]; however, it was natural to conjecture that no ADMSCs from aged mice or humans were used in their studies. Thus, our data were consistent with previous studies, and additional knowledge was provided for future studies.…”

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.…”

Adipose-derived stem cell-based optimization strategies for musculoskeletal regeneration: recent advances and perspectives

“…Fu et al injected an ADSC-Exos-hydrogel complex into the shoulders of rats in a rotator cuff injury model and observed enhanced rotator cuff repair and tendon-bone healing attributed to ADSC-Exos promoting the differentiation of tendon-derived stem cells [ 156 ]. Wang et al [ 157 ] demonstrated that the local administration of a fibrin gel containing ADSC-Exos could significantly prevent tear progression, enhance the biomechanical properties of the injured tendon, and promote high-quality tendon healing in a rabbit model of partial-thickness rotator cuff tears.…”