title: Repeated intra-articular injection of allogeneic mesenchymal stem cells causes an adverse response compared to autologous cells in the equine model.
abstract: Intra-articular injection of mesenchymal stem cells (MSCs) is efficacious in osteoarthritis therapy. A direct comparison of the response of the synovial joint to intra-articular injection of autologous versus allogeneic MSCs has not been performed. The objective of this study was to assess the clinical response to repeated intra-articular injection of allogeneic versus autologous MSCs prepared in a way to minimize xeno-contaminants in a large animal model.
  
  
  
  Intra-articular injections of bone marrow-derived, culture-expanded MSCs to a forelimb metacarpophalangeal joint were performed at week 0 and week 4 (six autologous; six autologous with xeno-contamination; six allogeneic). In the week following each injection, clinical and synovial cytology evaluations were performed.
  
  
  
  Following the first intra-articular injection, there were no differences in clinical parameters over time. Following the second intra-articular injection, there was a significant adverse response of the joint to allogeneic MSCs and autologous MSCs with xeno-contamination with elevated synovial total nucleated cell counts. There was also significantly increased pain from joints injected with autologous MSCs with xeno-contamination.
  
  
  
  Repeated intra-articular injection of allogeneic MSCs results in an adverse clinical response, suggesting there is immune recognition of allogeneic MSCs upon a second exposure.
authors.affiliation: Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Amanda-Jo
authors.initials: AJ
authors.lastname: Joswig
authors.affiliation: Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Mitchell
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Cummings
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Gwendolyn J
authors.initials: GJ
authors.lastname: Levine
authors.affiliation: Institute for Regenerative Medicine and Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, Texas A&M University, Temple, TX, 76502, USA.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Gregory
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Smith
authors.affiliation: Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA. awatts@cvm.tamu.edu.
authors.forename: Ashlee E
authors.initials: AE
authors.lastname: Watts
mesh_terms: D000818:Animals; D002417:Cattle; D005260:Female; D005552:Forelimb; D006736:Horses; D007270:Injections, Intra-Articular / Q000009:adverse effects*; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology; D008662:Metacarpophalangeal Joint / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous / Q000009:adverse effects*
chemical_list: D012710:Serum Albumin, Bovine
keywords: Bone marrow; FBS; Fetal bovine serum; Fetal calf serum; Flare; Horse; Intra-articular; Joint; MSC; Serum-free