BACKGROUND: The muscle quality of the rotator cuff (RC), measured by atrophy and fatty infiltration (FI), is a key determinant of outcomes in RC injury and repair. The ability to regenerate muscle after repair has been shown to be limited. PURPOSE: To determine if there is a source of resident endogenous stem cells, fibroadipogenic progenitor cells (FAPs), within RC injury patients, and if these cells are capable of adipogenic, fibrogenic, and pro-myogenic differentiation. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 20 patients between the ages of 40 and 75 years with partial- or full-thickness RC tears of the supraspinatus and evidence of atrophy and FI Goutallier grade 1, 2, or 3 were selected from 2 surgeons at an orthopaedic center. During the surgical repair procedure, supraspinatus muscle biopsy specimens were obtained for analysis as were deltoid muscle biopsy specimens to serve as the control. FAPs and satellite cells were quantified using fluorescence-activated cell sorting. Muscle FI and fibrosis was quantified using Oil Red O and Masson trichrome staining. FAP differentiation and gene expression profiles were compared across tear sizes after culture in adipogenic, fibrogenic, and beta-3 agonist (amibegron) conditions. Analysis of variance was used for statistical comparisons between groups, with P < .05 as statistically significant. RESULTS: Histologic analysis confirmed the presence of fat in biopsy specimens from patients with full-thickness tears. There were more FAPs in the full-thickness tear group compared with the partial-thickness tear group (9.43% ± 4.25% vs 3.84% ± 2.54%; P < .01). Full-thickness tears were divided by tear size, with patients with larger tears having significantly more FAPs than those with smaller tears. FAPs from muscles with full-thickness tendon tears had more adipogenic and fibrogenic potential than those with partial tears. Induction of a beige adipose tissue (BAT) phenotype in FAPs was possible, as demonstrated by increased expression of BAT markers and pro-myogenic genes including insulin-like growth factor 1 and follistatin. CONCLUSION: Endogenous FAPs are present within the RC and likely are the source of FI. These FAPs were increased in muscles with in larger tears but are capable of adopting a pro-myogenic BAT phenotype that could be utilized to improve muscle quality and patient function after RC repair.
BACKGROUND: The muscle quality of the rotator cuff (RC), measured by atrophy and fatty infiltration (FI), is a key determinant of outcomes in RC injury and repair. The ability to regenerate muscle after repair has been shown to be limited. PURPOSE: To determine if there is a source of resident endogenous stem cells, fibroadipogenic progenitor cells (FAPs), within RC injury patients, and if these cells are capable of adipogenic, fibrogenic, and pro-myogenic differentiation. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 20 patients between the ages of 40 and 75 years with partial- or full-thickness RC tears of the supraspinatus and evidence of atrophy and FI Goutallier grade 1, 2, or 3 were selected from 2 surgeons at an orthopaedic center. During the surgical repair procedure, supraspinatus muscle biopsy specimens were obtained for analysis as were deltoid muscle biopsy specimens to serve as the control. FAPs and satellite cells were quantified using fluorescence-activated cell sorting. Muscle FI and fibrosis was quantified using Oil Red O and Masson trichrome staining. FAP differentiation and gene expression profiles were compared across tear sizes after culture in adipogenic, fibrogenic, and beta-3 agonist (amibegron) conditions. Analysis of variance was used for statistical comparisons between groups, with P < .05 as statistically significant. RESULTS: Histologic analysis confirmed the presence of fat in biopsy specimens from patients with full-thickness tears. There were more FAPs in the full-thickness tear group compared with the partial-thickness tear group (9.43% ± 4.25% vs 3.84% ± 2.54%; P < .01). Full-thickness tears were divided by tear size, with patients with larger tears having significantly more FAPs than those with smaller tears. FAPs from muscles with full-thickness tendon tears had more adipogenic and fibrogenic potential than those with partial tears. Induction of a beige adipose tissue (BAT) phenotype in FAPs was possible, as demonstrated by increased expression of BAT markers and pro-myogenic genes including insulin-like growth factor 1 and follistatin. CONCLUSION: Endogenous FAPs are present within the RC and likely are the source of FI. These FAPs were increased in muscles with in larger tears but are capable of adopting a pro-myogenic BAT phenotype that could be utilized to improve muscle quality and patient function after RC repair.
Authors: Sonia Lee; Robert M Lucas; Drew A Lansdown; Lorenzo Nardo; Andrew Lai; Thomas M Link; Roland Krug; C Benjamin Ma Journal: J Shoulder Elbow Surg Date: 2015-03-26 Impact factor: 3.019
Authors: Koyal Garg; Catherine L Ward; Brady J Hurtgen; Jason M Wilken; Daniel J Stinner; Joseph C Wenke; Johnny G Owens; Benjamin T Corona Journal: J Orthop Res Date: 2014-09-18 Impact factor: 3.494
Authors: Xuhui Liu; Anne Y Ning; Nai Chen Chang; Hubert Kim; Robert Nissenson; Liping Wang; Brian T Feeley Journal: Muscles Ligaments Tendons J Date: 2016-05-19
Authors: Stefano Bartesaghi; Stefan Hallen; Li Huang; Per-Arne Svensson; Remi A Momo; Simonetta Wallin; Eva K Carlsson; Anna Forslöw; Patrick Seale; Xiao-Rong Peng Journal: Mol Endocrinol Date: 2015-01
Authors: Michael R Davies; Steven Garcia; Stanley Tamaki; Xuhui Liu; Solomon Lee; Anthony Jose; Jason H Pomerantz; Brian T Feeley Journal: J Orthop Res Date: 2018-03-09 Impact factor: 3.494
Authors: Dario R Lemos; Farshad Babaeijandaghi; Marcela Low; Chih-Kai Chang; Sunny T Lee; Daniela Fiore; Regan-Heng Zhang; Anuradha Natarajan; Sergei A Nedospasov; Fabio M V Rossi Journal: Nat Med Date: 2015-06-08 Impact factor: 53.440
Authors: A Uezumi; S Fukada; N Yamamoto; M Ikemoto-Uezumi; M Nakatani; M Morita; A Yamaguchi; H Yamada; I Nishino; Y Hamada; K Tsuchida Journal: Cell Death Dis Date: 2014-04-17 Impact factor: 8.469
Authors: Sydnee A Hyman; Isabella T Wu; Laura S Vasquez-Bolanos; Mackenzie B Norman; Mary C Esparza; Shannon N Bremner; Shanelle N Dorn; Ivan Ramirez; Donald C Fithian; John G Lane; Anshuman Singh; Samuel R Ward Journal: J Appl Physiol (1985) Date: 2021-10-14
Authors: Amil Sahai; Derek L Jones; Marcus Hughes; Alex Pu; Katrina Williams; Shama R Iyer; Chozha Rathinam; Derik L Davis; Richard M Lovering; Mohit N Gilotra Journal: J Orthop Res Date: 2022-03-03 Impact factor: 3.102
Authors: Michael R Davies; Hannah Chi; Gurbani Kaur; Mengyao Liu; C Benjamin Ma; Hubert T Kim; Xuhui Liu; Brian T Feeley Journal: Am J Sports Med Date: 2021-11-15 Impact factor: 7.010
Authors: Xuhui Liu; Mengyao Liu; Lawrence Lee; Michael Davies; Zili Wang; Hubert Kim; Brian T Feeley Journal: J Orthop Res Date: 2020-10-06 Impact factor: 3.494
Authors: Obiajulu Agha; Agustin Diaz; Michael Davies; Hubert T Kim; Xuhui Liu; Brian T Feeley Journal: Ann N Y Acad Sci Date: 2020-07-29 Impact factor: 5.691
Authors: Michael R Davies; Gurbani Kaur; Xuhui Liu; Francisco Gomez Alvarado; Prashant Nuthalapati; Mengyao Liu; Agustin Diaz; Jeffrey C Lotz; Jeannie F Bailey; Brian T Feeley Journal: N Am Spine Soc J Date: 2021-04-20