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Exposure of a tendon extracellular matrix to synovial fluid triggers endogenous and engrafted cell death: A mechanism for failed healing of intrathecal tendon injuries

Garvican, E R; Salavati, M; Smith, R K W; Dudhia, J

Authors

E R Garvican

M Salavati

R K W Smith

J Dudhia



Abstract

Aim: The purpose of this study was to investigate the effect of normal synovial fluid (SF) on exposed endogenous tendon-derived cells (TDC) and engrafted mesenchymal stem cells (MSCs) within the tendon extracellular matrix.
Methods: Explants from equine superficial digital flexor (extra-synovial) and deep digital flexor tendons (DDFT) from the compressed, intra-synovial and the tensile, extra-synovial regions were cultured in allogeneic or autologous SF-media. Human hamstring explants were cultured in allogeneic SF. Explant viability was assessed by staining. Proliferation of equine monolayer MSCs and TDCs in SF-media and co-culture with DDFT explants was determined by alamarblue®. Non-viable Native Tendon matrices (NNTs) were re-populated with MSCs or TDCs and cultured in SF-media. Immunohistochemical staining of tendon sections for the apoptotic proteins caspase-3, -8 and -9 was performed.
Results: Contact with autologous or allogeneic SF resulted in rapid death of resident tenocytes in equine and human tendon. SF did not affect the viability of equine epitenon cells, or of MSCs and TDCs in monolayer or indirect explant co-culture. MSCs and TDCs, engrafted into NNTs, died when cultured in SF. Caspase-3, -8 and -9 expression was greatest in SDFT explants exposed to allogeneic SF.
Conclusions: The efficacy of cells administered intra-synovially for tendon lesion repair is likely to be limited, since once incorporated into the matrix, cells become vulnerable to the adverse effects of SF. These observations could account for the poor success rate of intra-synovial tendon healing following damage to the epitenon and contact with SF, common with most soft tissue intra-synovial pathologies.

Citation

Garvican, E. R., Salavati, M., Smith, R. K. W., & Dudhia, J. (2016). Exposure of a tendon extracellular matrix to synovial fluid triggers endogenous and engrafted cell death: A mechanism for failed healing of intrathecal tendon injuries. Connective Tissue Research, 58(5), 438-446. https://doi.org/10.1080/03008207.2016.1245726

Journal Article Type Article
Acceptance Date Oct 3, 2016
Publication Date Oct 11, 2016
Deposit Date Oct 15, 2016
Publicly Available Date Mar 28, 2024
Journal Connective Tissue Research
Print ISSN 0300-8207
Publisher Taylor and Francis
Peer Reviewed Peer Reviewed
Volume 58
Issue 5
Pages 438-446
DOI https://doi.org/10.1080/03008207.2016.1245726
Public URL https://rvc-repository.worktribe.com/output/1395235