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

Monika L Bayer, Louise Bang, Maren Hoegberget-Kalisz, Rene B Svensson, Jens L Olesen, Mads M Karlsson, Peter Schjerling, Ylva Hellsten, Birgitte Hoier, S Peter Magnusson, Michael Kjaer

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.-Bayer, M. L., Bang, L., Hoegberget-Kalisz, M., Svensson, R. B., Olesen, J. L., Karlsson, M. M., Schjerling, P., Hellsten, Y., Hoier, B., Magnusson, S. P., Kjaer, M. Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans.

OriginalsprogEngelsk
TidsskriftF A S E B Journal
Vol/bind33
Udgave nummer9
Sider (fra-til)10369-10382
Antal sider14
ISSN0892-6638
DOI
StatusUdgivet - sep. 2019

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Exudates and Transudates
Connective Tissue
Muscle
Tissue
Muscles
Fibroblasts
Wounds and Injuries
Cell culture
Blood
Genes
Myoblasts
Angiogenesis Inducing Agents
Gene expression
Intercellular Signaling Peptides and Proteins
Repair
Cells
Cytokines
Gene Expression Profiling
Plasmas
Transcriptome

Citer dette

Bayer, M. L., Bang, L., Hoegberget-Kalisz, M., Svensson, R. B., Olesen, J. L., Karlsson, M. M., ... Kjaer, M. (2019). Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans. F A S E B Journal, 33(9), 10369-10382. https://doi.org/10.1096/fj.201900542R
Bayer, Monika L ; Bang, Louise ; Hoegberget-Kalisz, Maren ; Svensson, Rene B ; Olesen, Jens L ; Karlsson, Mads M ; Schjerling, Peter ; Hellsten, Ylva ; Hoier, Birgitte ; Magnusson, S Peter ; Kjaer, Michael. / Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans. I: F A S E B Journal. 2019 ; Bind 33, Nr. 9. s. 10369-10382.
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title = "Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans",
abstract = "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.-Bayer, M. L., Bang, L., Hoegberget-Kalisz, M., Svensson, R. B., Olesen, J. L., Karlsson, M. M., Schjerling, P., Hellsten, Y., Hoier, B., Magnusson, S. P., Kjaer, M. Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans.",
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Bayer, ML, Bang, L, Hoegberget-Kalisz, M, Svensson, RB, Olesen, JL, Karlsson, MM, Schjerling, P, Hellsten, Y, Hoier, B, Magnusson, SP & Kjaer, M 2019, 'Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans', F A S E B Journal, bind 33, nr. 9, s. 10369-10382. https://doi.org/10.1096/fj.201900542R

Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans. / Bayer, Monika L; Bang, Louise; Hoegberget-Kalisz, Maren; Svensson, Rene B; Olesen, Jens L; Karlsson, Mads M; Schjerling, Peter; Hellsten, Ylva; Hoier, Birgitte; Magnusson, S Peter; Kjaer, Michael.

I: F A S E B Journal, Bind 33, Nr. 9, 09.2019, s. 10369-10382.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 - Hoier, Birgitte

AU - Magnusson, S Peter

AU - Kjaer, Michael

PY - 2019/9

Y1 - 2019/9

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.-Bayer, M. L., Bang, L., Hoegberget-Kalisz, M., Svensson, R. B., Olesen, J. L., Karlsson, M. M., Schjerling, P., Hellsten, Y., Hoier, B., Magnusson, S. P., Kjaer, M. Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans.

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.-Bayer, M. L., Bang, L., Hoegberget-Kalisz, M., Svensson, R. B., Olesen, J. L., Karlsson, M. M., Schjerling, P., Hellsten, Y., Hoier, B., Magnusson, S. P., Kjaer, M. Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans.

KW - fibroblast

KW - fibrosis

KW - inflammation

KW - myoblast

KW - trauma

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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

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ER -