Purpose
To compare the efficacy of mesenchymal stem cell (MSC) exosomes with hyaluronic acid
(HA) against HA alone for functional cartilage regeneration in a rabbit osteochondral
defect model.
Methods
Critical-size osteochondral defects (4.5-mm diameter and 1.5-mm depth) were created
on the trochlear grooves in the knees of 18 rabbits and were randomly allocated to
2 treatment groups: (1) exosomes and HA combination and (2) HA alone. Three 1-mL injections
of either exosomes and HA or HA alone were administered intra-articularly immediately
after surgery and thereafter at 7 and 14 days after surgery. At 6 and 12 weeks, gross
evaluation, histologic and immunohistochemical analysis, and scoring were performed.
The functional biomechanical competence of the repaired cartilage also was evaluated.
Results
Compared with defects treated with HA, defects treated with exosomes and HA showed
significant improvements in macroscopic scores (P = .032; P = .001) and histologic scores (P = .005; P < .001) at 6 and 12 weeks, respectively. Defects treated with exosomes and HA also
demonstrated improvements in mechanical properties compared with HA-treated defects,
with significantly greater Young’s moduli (P < .05) and stiffness (P < .05) at 6 and 12 weeks. By 12 weeks, the newly-repaired tissues in defects treated
with exosomes and HA composed mainly of hyaline cartilage that are mechanically and
structurally superior to that of HA-treated defects and demonstrated mechanical properties
that approximated that of adjacent native cartilage (P > .05). In contrast, HA-treated defects showed some repair at 6 weeks, but this was
not sustained, as evidenced by significant deterioration of histologic scores (P = .002) and a plateau in mechanical properties from 6 to 12 weeks.
Conclusions
This study shows that the combination of MSC exosomes and HA administered at a clinically
acceptable frequency of 3 intra-articular injections can promote sustained and functional
cartilage repair in a rabbit post-traumatic cartilage defect model, when compared
with HA alone.
Clinical Relevance
Human MSC exosomes and HA administered in combination promote functional cartilage
repair and may represent a promising cell-free therapy for cartilage repair in patients.
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Article info
Publication history
Published online: April 14, 2020
Accepted:
March 17,
2020
Received:
August 14,
2019
Footnotes
See commentary on page 2229
The authors report the following potential conflicts of interest or sources of funding: S.K.L. holds founder shares in Paracrine Therapeutics Pte Ltd. This work was supported by grants from National Medical Research Council Singapore (NMRC/CNIG/1168/2017 and NMRC/CIRG/1480/2017). R.C.L. and S.K.L. are supported by the Agency for Science, Technology and Research (A∗STAR), Singapore. Full ICMJE author disclosure forms are available for this article online, as supplementary material.
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© 2020 by the Arthroscopy Association of North America
