TY - JOUR

T1 - Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans

AU - Bayer, Monika L

AU - Bang, Louise

AU - Hoegberget-Kalisz, Maren

AU - Svensson, Rene B

AU - Olesen, Jens L

AU - Karlsson, Mads M

AU - Schjerling, Peter

AU - Hellsten, Ylva

AU - Høier, Birgitte

AU - Magnusson, S Peter

AU - Kjær, Michael

N1 - CURIS 2019 NEXS 214

PY - 2019

Y1 - 2019

N2 - Traumatic strain injury in skeletal muscle is often associated with fluid accumulation at the site of rupture, but the role of this injury exudate (EX) in cellular responses and healing is unknown. We aimed to characterize the EX sampled from human hamstring or calf muscles following a strain injury (n = 12). The cytokine and growth-factor profile, gene expression, and transcriptome analysis of EX-derived cells were compared with blood taken simultaneously from the same individuals. Cellular responses to the EX were tested in 3-dimensional (3D) culture based on primary human fibroblasts and myoblasts isolated from hamstring muscles. The EX contained a highly proinflammatory profile with a substantial expression of angiogenic factors. The proinflammatory profile was present in samples taken early postinjury and in samples aspirated several weeks postinjury, suggesting persistent inflammation. Cells derived from the EX demonstrated an increased expression of fibrogenic, adipogenic, and angiogenesis-related genes in comparison with blood cells. The injury EX stimulated fibroblast proliferation 2-fold compared with plasma, whereas such an effect was not seen for myoblasts. Finally, in 3D cell culture, the EX induced an up-regulation of connective tissue-related genes. In summary, EX formation following a muscle-strain injury stimulates fibroblast proliferation and the synthesis of connective tissue in fibroblasts. This suggests that the EX promotes an acute tissue-healing response but potentially also contributes to the formation of fibrotic tissue in the later phases of tissue repair.

AB - Traumatic strain injury in skeletal muscle is often associated with fluid accumulation at the site of rupture, but the role of this injury exudate (EX) in cellular responses and healing is unknown. We aimed to characterize the EX sampled from human hamstring or calf muscles following a strain injury (n = 12). The cytokine and growth-factor profile, gene expression, and transcriptome analysis of EX-derived cells were compared with blood taken simultaneously from the same individuals. Cellular responses to the EX were tested in 3-dimensional (3D) culture based on primary human fibroblasts and myoblasts isolated from hamstring muscles. The EX contained a highly proinflammatory profile with a substantial expression of angiogenic factors. The proinflammatory profile was present in samples taken early postinjury and in samples aspirated several weeks postinjury, suggesting persistent inflammation. Cells derived from the EX demonstrated an increased expression of fibrogenic, adipogenic, and angiogenesis-related genes in comparison with blood cells. The injury EX stimulated fibroblast proliferation 2-fold compared with plasma, whereas such an effect was not seen for myoblasts. Finally, in 3D cell culture, the EX induced an up-regulation of connective tissue-related genes. In summary, EX formation following a muscle-strain injury stimulates fibroblast proliferation and the synthesis of connective tissue in fibroblasts. This suggests that the EX promotes an acute tissue-healing response but potentially also contributes to the formation of fibrotic tissue in the later phases of tissue repair.

KW - Faculty of Science

KW - Trauma

KW - Inflammation

KW - Fibrosis

KW - Fibroblast

KW - Myoblast

U2 - 10.1096/fj.201900542R

DO - 10.1096/fj.201900542R

M3 - Journal article

C2 - 31211922

VL - 33

SP - 10369

EP - 10382

JO - F A S E B Journal

JF - F A S E B Journal

SN - 0892-6638

IS - 9

ER -