T lymphocytes are not required for the development of fatty degeneration after rotator cuff tear

Abstract

Objectives Rotator cuff tears are among the most common and debilitating upper extremity injuries. Chronic cuff tears result in atrophy and an infiltration of fat into the muscle, a condition commonly referred to as ‘fatty degeneration’. While stem cell therapies hold promise for the treatment of cuff tears, a suitable immunodeficient animal model that could be used to study human or other xenograft-based therapies for the treatment of rotator cuff injuries had not previously been identified.Methods A full-thickness, massive supraspinatus and infraspinatus tear was induced in adult T-cell deficient rats. We hypothesised that, compared with controls, 28 days after inducing a tear we would observe a decrease in muscle force production, an accumulation of type IIB fibres, and an upregulation in the expression of genes involved with muscle atrophy, fibrosis and inflammation.Results Chronic cuff tears in nude rats resulted in a 30% to 40% decrease in muscle mass, a 23% reduction in production of muscle force, and an induction of genes that regulate atrophy, fibrosis, lipid accumulation, inflammation and macrophage recruitment. Marked large lipid droplet accumulation was also present.Conclusions The extent of degenerative changes in nude rats was similar to what was observed in T-cell competent rats. T cells may not play an important role in regulating muscle degeneration following chronic muscle unloading. The general similarities between nude and T-cell competent rats suggest the nude rat is likely an appropriate preclinical model for the study of xenografts that have the potential to enhance the treatment of chronically torn rotator cuff muscles.Cite this article: Bone Joint Res 2014;3:262–72.

Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear

“…Despite the location of SVFCs within adipose tissue, we did not find any human β2M or Alu + adipocytes within torn rotator cuff muscles, and we did not detect any changes in total lipid content between groups. The abundance of total triglyceride content of muscles in the current study is consistent with levels observed in previous rat studies [8, 9]. Although there were no differences between groups with regards to lipid content, there was a trend towards an improvement in muscle fiber sF o production in the 3×10 6 cell group, indicating that the treatment with SVFCs did not exacerbate fatty degeneration within these muscles.…”

“…Chronic fibrosis after rotator cuff tear leads to increased muscle stiffness and tension at the repair site [4], and along with the poor quality of the muscle due to atrophy and fatty infiltration [8], the potential for healing of torn rotator cuff muscles even after repair remains low. SVFC transplantation has been associated with a reduction in fibrosis and improved regeneration in other tissue injury and disease models, such as liver injury [13], Peyronie's disease [14], myocardial infarctions [15], and Dupuytren's disease [16], and supports our finding of reduced fibrosis after rotator cuff tear.…”

“…Although T-cell deficient rats develop fatty degeneration in a similar fashion to immunocompetent rats [8], no rat model develops the extent of fatty degeneration as seen in humans [21–23]. We chose a single time point of two weeks following repair and injection for our measurements and did not assess muscle function or SVFC viability past this time.…”

“…Four-month-old male athymic nude rats (NIH- Foxn1 rnu ) that lack a specific immune system were obtained from Charles River Laboratories (Wilmington, MA, USA). This animal model is commonly used for the study of xenografts, and we have previously demonstrated that nude rats develop fatty degeneration in a similar fashion to immune competent rats [8]. Rats were assigned to either serve as vehicle-treated controls or receive injections of SVFCs at a dose of either 3×10 5 cells or 3×10 6 cells in a randomized fashion.…”

“…Single fiber contractility was performed as previously described [8, 9]. The cross sectional area (CSA) of fibers was measured, and maximum isometric force (F o ) was elicited by immersing the fiber in a high calcium solution.…”