Abstract
BackgroundAdipose tissue is a promising source of mesenchymal stromal cells (MSCs) for the treatment of tendon disease. The goal of this study was to assess the effect of a single intralesional implantation of adipose tissue-derived mesenchymal stromal cells (AT-MSCs) on artificial lesions in equine superficial digital flexor tendons (SDFTs).MethodsDuring this randomized, controlled, blinded experimental study, either autologous cultured AT-MSCs suspended in autologous inactivated serum (AT-MSC-serum) or autologous inactivated serum (serum) were injected intralesionally 2 weeks after surgical creation of centrally located SDFT lesions in both forelimbs of nine horses. Healing was assessed clinically and with ultrasound (standard B-mode and ultrasound tissue characterization) at regular intervals over 24 weeks. After euthanasia of the horses the SDFTs were examined histologically, biochemically and by means of biomechanical testing.ResultsAT-MSC implantation did not substantially influence clinical and ultrasonographic parameters. Histology, biochemical and biomechanical characteristics of the repair tissue did not differ significantly between treatment modalities after 24 weeks. Compared with macroscopically normal tendon tissue, the content of the mature collagen crosslink hydroxylysylpyridinoline did not differ after AT-MSC-serum treatment (p = 0.074) while it was significantly lower (p = 0.027) in lesions treated with serum alone. Stress at failure (p = 0.048) and the modulus of elasticity (p = 0.001) were significantly lower after AT-MSC-serum treatment than in normal tendon tissue.ConclusionsThe effect of a single intralesional injection of cultured AT-MSCs suspended in autologous inactivated serum was not superior to treatment of surgically created SDFT lesions with autologous inactivated serum alone in a surgical model of tendinopathy over an observation period of 22 weeks. AT-MSC treatment might have a positive influence on collagen crosslinking of remodelling scar tissue. Controlled long-term studies including naturally occurring tendinopathies are necessary to verify the effects of AT-MSCs on tendon disease.
Highlights
Adipose tissue is a promising source of mesenchymal stromal cells (MSCs) for the treatment of tendon disease
The current study shows that a single treatment with 10 × 106 Adipose derived (AT)-MSCs suspended in inactivated autologous serum does not have a lasting effect on signs of inflammation and does not substantially improve ultrasonographic histologic, biochemical or biomechanical characteristics of surgically created superficial digital flexor tendon (SDFT) core lesions over a 24-week period compared with inactivated autologous serum alone
The effect of a single intralesional injection of cultured adipose tissue-derived mesenchymal stromal cells (AT-MSCs) suspended in autologous inactivated serum was not superior to the treatment of surgically created SDFT lesions with autologous inactivated serum alone in a surgical model of tendinopathy over an observation period of 22 weeks
Summary
Adipose tissue is a promising source of mesenchymal stromal cells (MSCs) for the treatment of tendon disease. The goal of this study was to assess the effect of a single intralesional implantation of adipose tissue-derived mesenchymal stromal cells (AT-MSCs) on artificial lesions in equine superficial digital flexor tendons (SDFTs). The superficial digital flexor tendon (SDFT), which is located at the palmar aspect of the limb, acts to store and release elastic energy and is subject to strains close to its functional limits [7, 8]. It is hypothesized that the injected cells may either differentiate into cells capable of synthesizing tendon matrix—that is, have a direct regenerative effect [16,17,18,19,20]—or act by a paracrine effect through the release of trophic mediators, growth factors and immunomodulatory, angiogenic as well as anti-apoptotic substances [21,22,23,24,25,26]
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