title: Clinicopathologic findings following intra-articular injection of autologous and allogeneic placentally derived equine mesenchymal stem cells in horses.
abstract: OBJECTIVE
  The development of an allogeneic mesenchymal stem cell (MSC) product to treat equine disorders would be useful; however, there are limited in vivo safety data for horses. We hypothesized that the injection of self (autologous) and non-self (related allogeneic or allogeneic) MSC would not elicit significant alterations in physical examination, gait or synovial fluid parameters when injected into the joints of healthy horses.
  
  
  METHODS
  Sixteen healthy horses were used in this study. Group 1 consisted of foals (n = 6), group 2 consisted of their dams (n = 5) and group 3 consisted of half-siblings (n = 5) to group 1 foals. Prior to injection, MSC were phenotyped. Placentally derived MSC were injected into contralateral joints and MSC diluent was injected into a separate joint (control). An examination, including lameness evaluation and synovial fluid analysis, was performed at 0, 24, 48 and 72 h post-injection.
  
  
  RESULTS
  MSC were major histocompatibility complex (MHC) I positive, MHC II negative and CD86 negative. Injection of allogeneic MSC did not elicit a systemic response. Local responses such as joint swelling or lameness were minimal and variable. Intra-articular MSC injection elicited marked inflammation within the synovial fluid (as measured by nucleated cell count, neutrophil number and total protein concentration). However, there were no significant differences between the degree and type of inflammation elicited by self and non-self-MSC.
  
  
  CONCLUSIONS
  The healthy equine joint responds similarly to a single intra-articular injection of autologous and allogeneic MSC. This pre-clinical safety study is an important first step in the development of equine allogeneic stem cell therapies.
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of California, Davis, California 95616, USA.
authors.forename: Danielle D
authors.initials: DD
authors.lastname: Carrade
authors.forename: Sean D
authors.initials: SD
authors.lastname: Owens
authors.forename: Larry D
authors.initials: LD
authors.lastname: Galuppo
authors.forename: Martin A
authors.initials: MA
authors.lastname: Vidal
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Ferraro
authors.forename: Fred
authors.initials: F
authors.lastname: Librach
authors.forename: Sabine
authors.initials: S
authors.lastname: Buerchler
authors.forename: Michael S
authors.initials: MS
authors.lastname: Friedman
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Walker
authors.forename: Dori L
authors.initials: DL
authors.lastname: Borjesson
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006736:Horses; D007270:Injections, Intra-Articular; D045164:Mesenchymal Stem Cell Transplantation; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D013582:Synovial Fluid / Q000737:chemistry
chemical_list: D051940:B7-2 Antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II