Tensile Loaded Tissue-Engineered Human Tendon Constructs Stimulate Myotube Formation
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Tensile Loaded Tissue-Engineered Human Tendon Constructs Stimulate Myotube Formation. / Tsuchiya, Yoshifumi; Svensson, René B.; Yeung, Ching Yan Chloé; Schjerling, Peter; Kjaer, Michael.
In: Tissue Engineering - Part A, Vol. 29, No. 9-10, 2023, p. 292-305.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Tensile Loaded Tissue-Engineered Human Tendon Constructs Stimulate Myotube Formation
AU - Tsuchiya, Yoshifumi
AU - Svensson, René B.
AU - Yeung, Ching Yan Chloé
AU - Schjerling, Peter
AU - Kjaer, Michael
N1 - Publisher Copyright: Copyright © 2023, Mary Ann Liebert, Inc.
PY - 2023
Y1 - 2023
N2 - Skeletal muscle possesses adaptability to mechanical loading and regenerative potential following muscle injury due to muscle stem cell activity. So far, it is known that muscle stem cell activity is supported by the roles of several interstitial cells within skeletal muscle in response to muscle damage. The adjacent tendon is also exposed to repetitive mechanical loading and possesses plasticity like skeletal muscle. However, the interplay between the skeletal muscle and adjacent tendon tissue has not been fully investigated. In this study, we tested whether factors released by three-dimensional engineered human tendon constructs in response to uniaxial tensile loading can stimulate the proliferation and differentiation of human-derived myogenic cells (myoblasts). Tendon constructs were subjected to repetitive mechanical loading (4% strain at 0.5 Hz for 4 h) and nonrepetitive loading (0% strain at 0 Hz for 4 h), and the conditioned media from mechanically loaded and nonmechanically loaded control constructs were applied to myoblasts. Immunofluorescence analysis revealed both an increase of myotube fusion index (≥5 nuclei within one desmin+ myotube) and the myotube diameter when conditioned medium from mechanically loaded tendon constructs was applied. Myostatin, myosin heavy chain 7, and AXIN2 gene expressions were downregulated in myotubes treated with conditioned medium from mechanically loaded tendon constructs. However, proliferative potential (number of Ki67+ and bromodeoxyuridine+ myoblasts) did not differ between the two groups. These results indicate that tendon fibroblasts enhance myotube formation by mechanical loading-induced factors. Our finding suggests that mechanical loading affects the signaling interplay between skeletal muscle and tendon tissue and is thus important for musculoskeletal tissue development and regeneration in humans. The interplay between satellite cells and various types of resident cells within the skeletal muscle for muscle regeneration has been extensively studied. However, even though tendon tissue is located adjacent to skeletal muscle tissue and cells in these tissues are exposed to repetitive mechanical loading together, the interaction between muscle and tendon tissues for muscle regeneration remains to be elucidated. In this study, we report that the conditioned media from engineered human tendon tissues undergoing repetitive tensile mechanical loading enhanced myotube formation. Our in vitro findings extend the fundamental understanding of the crosstalk between adjacent tissues of the muscle-tendon unit.
AB - Skeletal muscle possesses adaptability to mechanical loading and regenerative potential following muscle injury due to muscle stem cell activity. So far, it is known that muscle stem cell activity is supported by the roles of several interstitial cells within skeletal muscle in response to muscle damage. The adjacent tendon is also exposed to repetitive mechanical loading and possesses plasticity like skeletal muscle. However, the interplay between the skeletal muscle and adjacent tendon tissue has not been fully investigated. In this study, we tested whether factors released by three-dimensional engineered human tendon constructs in response to uniaxial tensile loading can stimulate the proliferation and differentiation of human-derived myogenic cells (myoblasts). Tendon constructs were subjected to repetitive mechanical loading (4% strain at 0.5 Hz for 4 h) and nonrepetitive loading (0% strain at 0 Hz for 4 h), and the conditioned media from mechanically loaded and nonmechanically loaded control constructs were applied to myoblasts. Immunofluorescence analysis revealed both an increase of myotube fusion index (≥5 nuclei within one desmin+ myotube) and the myotube diameter when conditioned medium from mechanically loaded tendon constructs was applied. Myostatin, myosin heavy chain 7, and AXIN2 gene expressions were downregulated in myotubes treated with conditioned medium from mechanically loaded tendon constructs. However, proliferative potential (number of Ki67+ and bromodeoxyuridine+ myoblasts) did not differ between the two groups. These results indicate that tendon fibroblasts enhance myotube formation by mechanical loading-induced factors. Our finding suggests that mechanical loading affects the signaling interplay between skeletal muscle and tendon tissue and is thus important for musculoskeletal tissue development and regeneration in humans. The interplay between satellite cells and various types of resident cells within the skeletal muscle for muscle regeneration has been extensively studied. However, even though tendon tissue is located adjacent to skeletal muscle tissue and cells in these tissues are exposed to repetitive mechanical loading together, the interaction between muscle and tendon tissues for muscle regeneration remains to be elucidated. In this study, we report that the conditioned media from engineered human tendon tissues undergoing repetitive tensile mechanical loading enhanced myotube formation. Our in vitro findings extend the fundamental understanding of the crosstalk between adjacent tissues of the muscle-tendon unit.
KW - cell communication
KW - mechanical loading
KW - muscle regeneration
KW - myoblasts
KW - satellite cells
KW - skeletal muscle
KW - tendon
KW - tendon fibroblasts
KW - tenocytes
U2 - 10.1089/ten.tea.2022.0173
DO - 10.1089/ten.tea.2022.0173
M3 - Journal article
C2 - 36680754
AN - SCOPUS:85159738756
VL - 29
SP - 292
EP - 305
JO - Tissue Engineering - Part A.
JF - Tissue Engineering - Part A.
SN - 1937-3341
IS - 9-10
ER -
ID: 371280329