title: Exposure of a tendon extracellular matrix to synovial fluid triggers endogenous and engrafted cell death: A mechanism for failed healing of intrathecal tendon injuries.
abstract: OBJECTIVE
  The purpose of this study was to investigate the effect of normal synovial fluid (SF) on exposed endogenous tendon-derived cells (TDCs) 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 (DDFTs) 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 the monolayer or indirect explant co-culture. MSCs and TDCs, engrafted into NNTs, died when cultured in SF. Caspase-3, -8, and -9 expression was the 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 vlnerable 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.
authors.affiliation: a Clinical Sciences and Services , The Royal Veterinary College , North Mymms , Hertfordshire , United Kingdom.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Garvican
authors.affiliation: a Clinical Sciences and Services , The Royal Veterinary College , North Mymms , Hertfordshire , United Kingdom.
authors.forename: Mazdak
authors.initials: M
authors.lastname: Salavati
authors.affiliation: a Clinical Sciences and Services , The Royal Veterinary College , North Mymms , Hertfordshire , United Kingdom.
authors.forename: Roger K W
authors.initials: RKW
authors.lastname: Smith
authors.affiliation: a Clinical Sciences and Services , The Royal Veterinary College , North Mymms , Hertfordshire , United Kingdom.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Dudhia
mesh_terms: D000818:Animals; D016923:Cell Death; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D006736:Horses; D006801:Humans; D013582:Synovial Fluid / Q000378:metabolism*; D013708:Tendon Injuries / Q000378:metabolism* / Q000473:pathology
keywords: Extracellular matrix; mesenchymal stem cell; synovial fluid; tendon; viability