title: Autologous and Allogeneic Equine Mesenchymal Stem Cells Exhibit Equivalent Immunomodulatory Properties In Vitro.
abstract: The use of allogeneic bone marrow-derived mesenchymal stem cells (BMDMSCs) may provide an effective alternative to autologous BMDMSCs for treatment of equine musculoskeletal injuries. However, concerns have been raised regarding the potential safety and effectiveness of allogeneic BMDMSCs. We conducted studies to assess the immunological properties of equine allogeneic BMDMSCs compared with those of autologous BMDMSCs. For assessment of inherent immunogenicity, the relative ability of allogeneic and autologous BMDMSCs to stimulate spontaneous proliferation of equine lymphocytes was compared. The immunosuppressive activity of the two cell types was evaluated by adding autologous or allogeneic BMDMSCs to activated lymphocytes and assessing suppression of lymphocyte proliferation and IFNγ production. Fifty-six allogeneic and 12 autologous combinations were evaluated. Studies were also done to elucidate mechanisms by which equine mesenchymal stem cells (MSCs) suppress lymphocyte function. Potential mechanisms evaluated included production of prostaglandin E2(PGE2), nitric oxide, transforming growth factor-beta, and indoleamine 2,3-dioxygenase. We found that autologous and allogeneic BMDMSCs both induced mild but equivalent levels of spontaneous lymphocyte activation in vitro. In in vitro assays assessing the ability of BMDMSCs to suppress activated lymphocytes, both allogeneic and autologous BMDMSCs suppressed T cell proliferation and IFNγ production to an equal degree. The primary mechanism of equine BMDMSC suppression of T cells was mediated by PGE2. We concluded that allogeneic and autologous BMDMSCs are equivalent in terms of their immunomodulatory properties, and stimulated peripheral blood mononuclear cells appear to trigger the immunosuppressive properties of MSCs. Therefore, both cell types appear to have equal potency in modulating inflammatory processes related to acute or chronic musculoskeletal injuries in the horse.
authors.affiliation: 1 Orthopaedic Research Center, Colorado State University , Fort Collins, Colorado.
authors.forename: Aimée C
authors.initials: AC
authors.lastname: Colbath
authors.affiliation: 2 Clinical Sciences, Colorado State University , Fort Collins, Colorado.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Dow
authors.affiliation: 1 Orthopaedic Research Center, Colorado State University , Fort Collins, Colorado.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Phillips
authors.affiliation: 1 Orthopaedic Research Center, Colorado State University , Fort Collins, Colorado.
authors.forename: C Wayne
authors.initials: CW
authors.lastname: McIlwraith
authors.affiliation: 1 Orthopaedic Research Center, Colorado State University , Fort Collins, Colorado.|2 Clinical Sciences, Colorado State University , Fort Collins, Colorado.
authors.forename: Laurie R
authors.initials: LR
authors.lastname: Goodrich
mesh_terms: D001324:Autoantigens / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology; D008222:Lymphokines / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001324:Autoantigens; D008222:Lymphokines; C022780:allogenic effect factor
keywords: allogeneic; autologous; bone marrow-derived mesenchymal stem cell; immunomodulation; lymphocyte proliferation assay