The efficacy of mesenchymal stem cell (MSC) therapies is increasingly attributed to
paracrine secretion, particularly exosomes. Here, we investigate the effects of MSC
exosomes on pain severity and cartilage degeneration in an experimental model of temporomandibular
joint osteoarthritis (TMJ-OA). Exosomes were purified from human MSC conditioned medium.
OA of bilateral TMJs was induced in rats by intra-articular injection of monosodium
iodoacetate. Thereafter, weekly intra-articular injections of 100 µg of exosomes in
50µl of phosphate buffered saline (PBS) or equivalent volume of vehicle were given
over 2, 4 and 8 weeks. Analyses were performed by head withdrawal threshold (HWT)
measurement, micro-computed tomography, histology and immunohistochemistry, and Mankin
scoring. Early gene expression changes induced by MSC exosomes were measured by transcriptomic
analysis (using RT-PCR) of the condylar cartilage tissue. Comparison was made with
OA rats that received PBS, as well as with sham and age-matched native rats. Our results
showed that MSC exosomes attenuated the nociceptive response and reversed cartilage
degradation and subchondral bone loss in rats with TMJ-OA. Exosome-treated lesions
showed restoration of cartilage structure and subchondral bone integrity with improved
Mankin scores, compared to PBS-treated lesions. Suppression of inflammation and oxidative
damage in conjunction with enhanced cellular proliferation were observed. By 8 weeks,
exosome-treated rats showed HWT recovery to a level similar to the sham rats, and
displayed cartilage and subchondral bone restoration including appropriate condyle
cartilage thickness, cellularity, matrix deposition, and subchondral bone architecture
similar to that of sham control and closely resembled that of the native rats. Importantly,
no adverse reactions were observed in all animals. Taken together, our findings demonstrate
the efficacy of MSC exosomes to attenuate pain and reverse degeneration in an animal
model of TMJ-OA. This study provides the basis for future use of human MSC exosomes
as a ready-to-use and cell-free therapeutic for TMJ-OA.
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