title: vIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis.
abstract: BACKGROUND
  Recent efforts in osteoarthritis (OA) research have highlighted synovial inflammation and involvement of immune cells in disease onset and progression. We sought to establish the in-vivo immune response in collagenase-induced OA and investigate the ability of human mesenchymal stem cells (hMSCs) overexpressing viral interleukin 10 (vIL-10) to modulate immune populations and delay/prevent disease progression.
  
  
  METHODS
  Eight-week-old male C57BL/6 mice were injected with 1 U type VII collagenase over two consecutive days. At day 7, 20,000 hMSCs overexpressing vIL-10 were injected into the affected knee. Control groups comprised of vehicle, 20,000 untransduced or adNull-transduced MSCs or virus alone. Six weeks later knees were harvested for histological analysis and popliteal and inguinal lymph nodes for flow cytometric analysis.
  
  
  RESULTS
  At this time there was no significant difference in knee OA scores between any of the groups. A trend toward more damage in animals treated with hMSCs was observed. Interestingly there was a significant reduction in the amount of activated CD4 and CD8 T cells in the vIL-10-expressing hMSC group.
  
  
  CONCLUSIONS
  vIL-10-overexpressing hMSCs can induce long-term reduction in activated T cells in draining lymph nodes of mice with collagenase-induced OA. This could lead to reduced OA severity or disease progression over the long term.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Special Dental Care and Orthodontics, Erasmus MC, University Medical Centre, Room Ee1614, Erasmus MC, Wytemaweg 80, Rotterdam, 3015CN, The Netherlands. e.farrell@erasmusmc.nl.|Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland. e.farrell@erasmusmc.nl.
authors.forename: Eric
authors.initials: E
authors.lastname: Farrell
authors.affiliation: Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland.|Musculoskeletal Regeneration, AO Research Institute Davos (ARI), Davos, Switzerland.
authors.forename: Niamh
authors.initials: N
authors.lastname: Fahy
authors.affiliation: Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland.|College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.|Discipline of Pharmacology and Therapeutics, National University of Ireland Galway, Galway, Ireland.
authors.forename: Aideen E
authors.initials: AE
authors.lastname: Ryan
authors.affiliation: Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland.
authors.forename: Cathal O
authors.initials: CO
authors.lastname: Flatharta
authors.affiliation: Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland.|College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.|Orbsen Therapeutics Ltd, Galway, Ireland.
authors.forename: Lisa
authors.initials: L
authors.lastname: O'Flynn
authors.affiliation: Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland.|College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ritter
authors.affiliation: Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland.
authors.forename: J Mary
authors.initials: JM
authors.lastname: Murphy
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D017364:Collagenases; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D007719:Knee Joint / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019076:Transgenes
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10; D017364:Collagenases
keywords: Cell therapy; Collagenase-induced osteoarthritis; Gene therapy; Mesenchymal stem cell; Xenogeneic; vIL-10