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Rotator cuff tear state modulates self‐renewal and differentiation capacity of human skeletal muscle progenitor cells
Author(s) -
Thomas Kelsey A.,
Gibbons Michael C.,
Lane John G.,
Singh Anshuman,
Ward Samuel R.,
Engler Adam J.
Publication year - 2017
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.23453
Subject(s) - rotator cuff , myogenesis , tears , muscle atrophy , skeletal muscle , tendon , myosin , extracellular matrix , myocyte , medicine , progenitor cell , microbiology and biotechnology , anatomy , biology , stem cell , surgery
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.