title: Intradermal injections of equine allogeneic umbilical cord-derived mesenchymal stem cells are well tolerated and do not elicit immediate or delayed hypersensitivity reactions.
abstract: BACKGROUND AIMS. The use of allogeneic mesenchymal stem cells (MSC) to treat acute equine lesions would greatly expand equine cellular therapy options; however, the safety and antigenicity of these cells have not been well-studied. We hypothesized that equine allogeneic umbilical cord tissue (UCT)-derived MSC would not elicit acute graft rejection or a delayed-type hypersensitivity response when injected intradermally. METHODS. Six Quarterhorse yearlings received 12 intradermal injections (autologous MSC, allogeneic MSC, positive control and negative control, in triplicate) followed by the same series of 12 injections, 3-4 weeks later, at another site. Wheals were measured and palpated at 0.25, 4, 24, 48, 72 h and 7 days post-injection. Biopsies were obtained at 48 and 72 h and 7 days post-injection. Mixed leukocyte reactions were performed 1 week prior to the first injections and 3 weeks after the second injections. RESULTS. There were no adverse local or systemic responses to two intradermal injections of allogeneic MSC. MSC injection resulted in minor wheal formation, characterized by mild dermatitis, dermal edema and endothelial hyperplasia, that fully resolved by 48-72 h. No differences were noted between allogeneic and autologous MSC. The second injection of MSC did not elicit more significant physical or histomorphologic alterations compared with the first MSC injection. Neither allogeneic nor autologous UCT-derived MSC stimulated or suppressed baseline T-cell proliferation in vitro prior to or after two MSC administrations. CONCLUSIONS. Equine allogeneic UCT MSC may be safely administered intradermally on multiple occasions without eliciting a measurable cellular immune response.
authors: Departments of Pathology, Microbiology and Immunology, School of Veterinary, University of California, USA.
authors: Danielle D
authors: DD
authors: Carrade
authors: Verena K
authors: VK
authors: Affolter
authors: Catherine A
authors: CA
authors: Outerbridge
authors: Johanna L
authors: JL
authors: Watson
authors: Larry D
authors: LD
authors: Galuppo
authors: Sabine
authors: S
authors: Buerchler
authors: Vijay
authors: V
authors: Kumar
authors: Naomi J
authors: NJ
authors: Walker
authors: Dori L
authors: DL
authors: Borjesson
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006736:Horses; D006968:Hypersensitivity, Delayed / Q000209:etiology* / Q000517:prevention & control; D006969:Hypersensitivity, Immediate / Q000209:etiology* / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D011183:Postoperative Complications; D013601:T-Lymphocytes / Q000276:immunology; D014470:Umbilical Cord / Q000166:cytology