title: Perivascular Stem Cells Diminish Muscle Atrophy Following Massive Rotator Cuff Tears in a Small Animal Model.
abstract: 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.
  
  
  CONCLUSIONS
  Improved muscle quality in the setting of rotator cuff tears may increase the success rates of surgical repair and lead to superior clinical outcomes.
authors.affiliation: 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.
authors.forename: Claire D
authors.initials: CD
authors.lastname: Eliasberg
authors.forename: Ayelet
authors.initials: A
authors.lastname: Dar
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Jensen
authors.forename: Iain R
authors.initials: IR
authors.lastname: Murray
authors.forename: Winters R
authors.initials: WR
authors.lastname: Hardy
authors.forename: Tomasz J
authors.initials: TJ
authors.lastname: Kowalski
authors.forename: Cameron A
authors.initials: CA
authors.lastname: Garagozlo
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Natsuhara
authors.forename: Adam Z
authors.initials: AZ
authors.lastname: Khan
authors.forename: Owen J
authors.initials: OJ
authors.lastname: McBride
authors.forename: Peter I
authors.initials: PI
authors.lastname: Cha
authors.forename: Benjamin V
authors.initials: BV
authors.lastname: Kelley
authors.forename: Denis
authors.initials: D
authors.lastname: Evseenko
authors.forename: Brian T
authors.initials: BT
authors.lastname: Feeley
authors.forename: David R
authors.initials: DR
authors.lastname: McAllister
authors.forename: Bruno
authors.initials: B
authors.lastname: Péault
authors.forename: Frank A
authors.initials: FA
authors.lastname: Petrigliano
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D009133:Muscular Atrophy / Q000473:pathology / Q000628:therapy*; D000070636:Rotator Cuff Injuries / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells