title: Rotator cuff tear state modulates self-renewal and differentiation capacity of human skeletal muscle progenitor cells.
abstract: Full thickness rotator cuff tendon (RCT) tears have long-term effects on RC muscle atrophy and fatty infiltration, with lasting damage even after surgical tendon repair. Skeletal muscle progenitor cells (SMPs) are critical for muscle repair in response to injury, but the inability of RC muscles to recover from chronic RCT tear indicates possible deficits in repair mechanisms. Here we investigated if muscle injury state was a crucial factor during human SMP expansion and differentiation ex vivo. SMPs were isolated from muscles in patients with no, partial-thickness (PT), or full-thickness (FT) RCT tears. Despite using growth factors, physiological niche stiffness, and muscle-mimetic extracellular matrix (ECM) proteins, we found that SMPs isolated from human RC muscle with RCT tears proliferated slower but fused into myosin heavy chain (MHC)-positive myotubes at higher rates than SMPs from untorn RCTs. Proteomic analysis of RC muscle tissue revealed shifts in muscle composition with pathology, as muscle from massive RCT tears had increased ECM deposition compared with no tear RC muscle. Together these data imply that the remodeled niche in a torn RCT primes SMPs not for expansion but for differentiation, thus limiting longer-term self-renewal necessary for regeneration after surgical repair. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1816-1823, 2017.
authors.affiliation: Biomedical Sciences Program, UC San Diego, La Jolla, California, 92093.
authors.forename: Kelsey A
authors.initials: KA
authors.lastname: Thomas
authors.affiliation: Department of Bioengineering, UC San Diego, La Jolla, California, 92093.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Gibbons
authors.affiliation: Department of Orthopaedic Surgery, UC San Diego, La Jolla, California, 92093.
authors.forename: John G
authors.initials: JG
authors.lastname: Lane
authors.affiliation: Department of Orthopaedic Surgery, Kaiser Permanente San Diego, San Diego, California, 92111.
authors.forename: Anshuman
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Orthopaedic Surgery, UC San Diego, La Jolla, California, 92093.|Department of Radiology, UC San Diego, La Jolla, California, 92093.
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Ward
authors.affiliation: Biomedical Sciences Program, UC San Diego, La Jolla, California, 92093.|Department of Bioengineering, UC San Diego, La Jolla, California, 92093.|Sanford Consortium for Regenerative Medicine, La Jolla, California, 92037.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Engler
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000502:physiology*; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D000070636:Rotator Cuff Injuries / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D009124:Muscle Proteins
keywords: growth factors; hydrogels; mass spectrometry; proliferation; regenerative medicine