title: Stage-specific differences in secretory profile of mesenchymal stromal cells (MSCs) subjected to early- vs late-stage OA synovial fluid.
abstract: Although, mesenchymal stromal cells (MSCs) are being clinically investigated for their use in osteoarthritis (OA), it is unclear whether their postulated therapeutic properties are equally effective in the early- and late-stages of OA. In this study we investigated MSC cytokine secretion post-exposure to synovial fluid (SF), obtained from early- vs late-stage knee OA patients to justify a potential patient stratification strategy to maximize MSC-mediated treatment effects.
  
  
  
  Subjects were recruited and categorized into early- [Kellgren-Lawrence (KL) grade I/II, n = 12] and late-stage (KL-III/IV, n = 12) knee OA groups. SF samples were obtained, and their proteome was tested using multiplex assays, after 3-days culture, with and without MSCs. SFs cultured without MSCs were used as a baseline to identify MSC-secreted factors into SFs cultured with MSCs. Linear mixed-effect models and non-parametric tests were used to identify alterations in the MSC secretome during exposure to OA SF (3-days). MSCs cultured for 3-days in 0.5% fetal bovine serum (FBS)-supplemented medium were used to compare SF results with culture medium.
  
  
  
  Following exposure to OA SF, the MSC secretome contained proteins that are involved in tissue repair, angiogenesis, chemotaxis, matrix remodeling and the clotting process. However, chemokine (C-X-C motif) ligand-8 (CXCL8; chemoattractant), interleukin-6 (IL6) and chemokine (C-C motif) ligand 2 (CCL2) were elevated in the MSC-secretome in response to early- vs late-stage OA SF.
  
  
  
  Early- vs late-stage OA SF samples elicit a differential MSC secretome response, arguing for stratification of OA patients to maximize MSC-mediated therapeutic effects.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; The Arthritis Program, Toronto Western Hospital, Toronto, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Gómez-Aristizábal
authors.affiliation: The Arthritis Program, Toronto Western Hospital, Toronto, ON, Canada; Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, ON, Canada.
authors.forename: M A
authors.initials: MA
authors.lastname: Bakooshli
authors.affiliation: The Arthritis Program, Toronto Western Hospital, Toronto, ON, Canada; Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Kapoor
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, ON, Canada; Department of Biochemistry, University of Toronto, ON, Canada.
authors.forename: P M
authors.initials: PM
authors.lastname: Gilbert
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; The Arthritis Program, Toronto Western Hospital, Toronto, ON, Canada; Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada; Cell Therapy Program, University Health Network, Toronto, Canada. Electronic address: sowmya.viswanathan@uhnresearch.ca.
authors.forename: S
authors.initials: S
authors.lastname: Viswanathan
authors.affiliation: The Arthritis Program, Toronto Western Hospital, Toronto, ON, Canada; Division of Orthopaedic Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada. Electronic address: rajiv.gandhi@uhn.ca.
authors.forename: R
authors.initials: R
authors.lastname: Gandhi
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology*; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6
keywords: CXCL8; Cytokines; Mesenchymal stromal cells; Multiplex; Osteoarthritis; Synovial fluid