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Perivascular Stem Cells Diminish Muscle Atrophy Following Massive Rotator Cuff Tears in a Small Animal Model

Eliasberg, Claire D. MD; Dar, Ayelet PhD; Jensen, Andrew R. MD, MBE; Murray, Iain R. MD, PhD; Hardy, Winters R. PhD; Kowalski, Tomasz J. MD, PhD; Garagozlo, Cameron A. BA; Natsuhara, Kyle M. MD; Khan, Adam Z. MD; McBride, Owen J. BS; Cha, Peter I. BA; Kelley, Benjamin V. BA; Evseenko, Denis MD, PhD; Feeley, Brian T. MD; McAllister, David R. MD; Péault, Bruno PhD; Petrigliano, Frank A. MD

Journal of Bone & Joint Surgery - American Volume: 15 February 2017 - Volume 99 - Issue 4 - p 331–341
doi: 10.2106/JBJS.16.00645
Scientific Articles
Disclosures

Background: Rotator cuff tears are a common cause of shoulder pain and often necessitate operative repair. Muscle atrophy, fibrosis, and fatty infiltration can develop after rotator cuff tears, which may compromise surgical outcomes. This study investigated the regenerative potential of 2 human adipose-derived progenitor cell lineages in a murine model of massive rotator cuff tears.

Methods: Ninety immunodeficient mice were used (15 groups of 6 mice). Mice were assigned to 1 of 3 surgical procedures: sham, supraspinatus and infraspinatus tendon transection (TT), or TT and denervation via suprascapular nerve transection (TT + DN). Perivascular stem cells (PSCs) were harvested from human lipoaspirate and sorted using fluorescence-activated cell sorting into pericytes (CD146+ CD34 CD45 CD31) and adventitial cells (CD146 CD34+ CD45 CD31). Mice received no injection, injection with saline solution, or injection with pericytes or adventitial cells either at the time of the index procedure (“prophylactic”) or at 2 weeks following the index surgery (“therapeutic”). Muscles were harvested 6 weeks following the index procedure. Wet muscle weight, muscle fiber cross-sectional area, fibrosis, and fatty infiltration were analyzed.

Results: PSC treatment after TT (prophylactic or therapeutic injections) and after TT + DN (therapeutic injections) resulted in less muscle weight loss and greater muscle fiber cross-sectional area than was demonstrated for controls (p < 0.05). The TT + DN groups treated with pericytes at either time point or with adventitial cells at 2 weeks postoperatively had less fibrosis than the TT + DN controls. There was less fatty infiltration in the TT groups treated with pericytes at either time point or with adventitial cells at the time of surgery compared with controls.

Conclusions: Our findings demonstrated significantly less muscle atrophy in the groups treated with PSCs compared with controls. This suggests that the use of PSCs may have a role in the prevention of muscle atrophy without leading to increased fibrosis or fatty infiltration.

Clinical Relevance: Improved muscle quality in the setting of rotator cuff tears may increase the success rates of surgical repair and lead to superior clinical outcomes.

1Hospital for Special Surgery, New York, NY

2University of California, Los Angeles, Los Angeles, California

3University of Edinburgh, Edinburgh, United Kingdom

4University of California, Davis, Davis, California

5Washington University, St. Louis, Missouri

6University of Southern California, Los Angeles, California

7University of California, San Francisco, San Francisco, California

E-mail address for C.D. Eliasberg: eliasbergc@hss.edu

Copyright 2017 by The Journal of Bone and Joint Surgery, Incorporated
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