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. 2020 Sep;48(11):2660-2668.
doi: 10.1177/0363546520935855. Epub 2020 Jul 30.

Human Rotator Cuff Tears Have an Endogenous, Inducible Stem Cell Source Capable of Improving Muscle Quality and Function After Rotator Cuff Repair

Brian T Feeley  1   2 , Mengyao Liu  1   2 , C Benjamin Ma  1   2 , Obiajulu Agha  1   2 , Mya Aung  2 , Carlin Lee  1   2 , Xuhui Liu  1   2
Affiliations

Human Rotator Cuff Tears Have an Endogenous, Inducible Stem Cell Source Capable of Improving Muscle Quality and Function After Rotator Cuff Repair

Brian T Feeley et al. Am J Sports Med. 2020 Sep.

Abstract

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.

Keywords: fibroadipogenic progenitor; rotator cuff; shoulder; stem cell.

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Figures

Figure 1.
Figure 1.
Arthroscopic supraspinatus biopsy with a pituitary rongeur.
Figure 2.
Figure 2.
(A) Representative trichrome straining of supraspinatus (SS) and deltoid (DL) biopsy specimens. (B) There was a higher percentage of collagen staining in the full-thickness tears compared with the partial tear and DL. (C) Oil Red O evaluation of fatty infiltration (FI) of full-thickness and partial-thickness tears in the SS compared with the control DL. (D) Quantification of FI with significantly more fat in the full-thickness than the partial-thickness tears. (E) Typical immunostaining of full-thickness tears compared with partial tears. Green stains are laminin and red is stained for fibroadipogenic progenitors. *P < .05.
Figure 3.
Figure 3.
Fibroadipogenic progenitor (FAP) cell counts from supraspinatus biopsy specimens from different size rotator cuff (RC) tears using fluorescence-activated cell sorting. *P < .05 compared with partial tears; **P < .05 compared with small tear size.
Figure 4.
Figure 4.
(A) Treatment with fibrogenic and adipogenic media led to more fibrogenic and adipogenic differentiation in fibroadipogenic progenitor from full-thickness tears compared with partial tears. (B) Quantification of fibroblastic cells. (C) Quantification of adipocytes. (D) Treatment with amibegron results in increased beige fat differentiation, more so in FAPs from full-thickness tears compared with partial tears. (E) Quantification of beige fat differentiation. *P < .05.
Figure 5.
Figure 5.
Reverse transcription polymerase chain reaction analysis of gene expression of fibroadipogenic progenitors (FAPs) obtained from partial rotator cuff (RC) tears (top graph) and full RC tears (bottom graph) compared with FAPs obtained from the patient’s deltoid muscle after 2 weeks of treatment with either adipogenic media alone (black bars) or 10 μM amibegron (gray bars). Y axis represents logarithmic scale. *P < .05.
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References

    1. Bartesaghi S, Hallen S, Huang L, et al. Thermogenic activity of UCP1 in human white fat-derived beige adipocytes. Mol Endocrinol. 2015;29(1):130–139. - PMC - PubMed
    1. Braga M, Reddy ST, Vergnes L, et al. Follistatin promotes adipocytedifferentiation, browning, and energy metabolism. J Lipid Res. 2014;55(3):375–384. - PMC - PubMed
    1. Bryniarski AR, Meyer GA. Brown fat promotes muscle growth duringregeneration. J Orthop Res. 2019;37(8):1817–1826. - PMC - PubMed
    1. Cohen P, Levy JD, Zhang Y, et al. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell. 2014;156(1–2):304–316. - PMC - PubMed
    1. Collins CA, Zammit PS, Ruiz AP, et al. A population of myogenic stemcells that survives skeletal muscle aging. Stem Cells. 2007;25(4):885–894. - PubMed

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