Abstract
Although rotator cuff disease is a common cause of shoulder pain, there is still no treatment method that could halt or reveres its development and progression. The purpose of this study was to investigate the efficacy of umbilical cord-derived mesenchymal stem cells (UC MSCs) on the regeneration of a full-thickness rotator cuff defect (FTD) in a rat model. We injected either UC MSCs or saline to the FTD and investigated macroscopic, histological and biomechanical results and cell trafficking. Treatment with UC MSCs improved macroscopic appearance in terms of tendon thickness at two weeks, and inflammation, defect size, swelling/redness and connection surrounding tissue and slidability at four weeks compared to the saline group. Histologically, UC MSCs induced the tendon matrix formation recovering collagen organization, nuclear aspect ratio and orientation angle of fibroblast as well as suppressing cartilage-related glycosaminoglycan compared to saline group at four weeks. The UC MSCs group also improved ultimate failure load by 25.0% and 19.0% and ultimate stress by 27.3% and 26.8% at two and four weeks compared to saline group. UC MSCs labeled with PKH26 exhibited 5.3% survival at four weeks compared to three hours after injection. This study demonstrated that UC MSCs regenerated the FTD with tendon tissue similar properties to the normal tendon in terms of macroscopic, histological and biomechanical characteristics in a rat model.
Highlights
Shoulder pain results in over 4.5 million physician visits, and rotator cuff disease is the most common cause of shoulder pain accounting up to 70% of cases with approximately 300,000 operations each year in the United States [1, 2]
Tendon thickness score was significantly less in the umbilical cord-derived mesenchymal stem cells (UC mesenchymal stem cells (MSCs)) group in comparison with that in the saline group ant the total macroscopic score was significantly lower in the UC MSCs group, 7.25 ± 0.96, than in the saline group, 10.00 ± 1.15 (p = .005) at two weeks
The ultimate failure load in the UC MSCs group at four weeks was comparable with that of the control group; and 5) intratendinously injected UC MSCs disappeared over time, and 5.29% of those at three hours were retained in the tendon defect at four weeks after injection
Summary
Shoulder pain results in over 4.5 million physician visits, and rotator cuff disease is the most common cause of shoulder pain accounting up to 70% of cases with approximately 300,000 operations each year in the United States [1, 2]. Tendon regeneration using UC MSCs indicated no potential conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Current conservative treatments for rotator cuff disease include rest, non-steroidal antiinflammatory drugs, physical therapy and various kinds of injections [4, 5]. A considerable number of patients, 41%, showed persistent symptoms after 12 months of treatment [7]. These results may be attributed to the fact that those symptomatic treatments do not address the fundamental etiology of rotator cuff disease, most importantly tendon degeneration [8]. As tenocytes in degenerative tendon do not participate in the regeneration process [9], it would be momentous to investigate new biological strategies such as application of various cells, growth factors and cytokines to more adequately treat tendon degeneration [10]
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