Inflammatory and Immune Effects of Intra-Articular Mesenchymal Stem Cells in Horses

Mesenchymal stem cells have demonstrated anti-inflammatory and immunomodulatory capabilities as well as modest efficacy in animal models of joint injury, warranting further study as a potential treatment of equine joint disease. The goal of the study is to investigate the inflammatory and immune response to intra-articular injection of autologous, genetically modified (bone morphogenetic protein 2) autologous, allogeneic, and xenogeneic bone marrow-derived mesenchymal stem cells (MSC) in horses. The study group consisted of 6 five-year-old Thoroughbred mares, free of musculoskeletal disease in the fetlocks. The 4 fetlock joints were injected on day 0 with 15 million MSC from the described MSC groups and were assessed for 28 days for clinical and inflammatory parameters representing synovitis, swelling and pain. Arthroscopic examination and synovial biopsies were taken at day 60 post-injection for histologic and molecular analyses. On day 120, peripheral blood mononuclear cells were isolated from each horse and co-cultured with monolayers of each MSC group for analysis of CD4 positive cells via flow cytometry and cytokines via ELISA.There was no significant difference between autologous and genetically modified autologous MSC for any parameter examined and soluble gene product was detected for at least 2 days. Allogeneic and xenogeneic MSC produced a modest increase in peak of inflammation at 24 hours than either autologous MSC group. Most inflammatory parameters returned to baseline or control values within 7-14 days for all MSC groups. Arthroscopic examination revealed normal synovium with no grossly detrimental effect to the synovium or cartilage. Synovial histology demonstrated significantly increased inflammatory cells, lymphocyte perivascular cuffing and bone morphogenetic protein 2 antibody uptake for MSC injected joints compared to controls. Adaptive immunity was demonstrated upon re-exposure of peripheral blood mononuclear cells to xenogeneic MSC in co-culture but not for allogeneic MSC. Genetically engineered MSC can produce gene product to detectable synovial concentrations and did not result in greater inflammation warranting further investigation into the therapeutic potential of this cell therapy. Intra-articular MSC resulted in a moderate acute inflammatory joint response that was greater for allogeneic and xenogeneic MSC than autologous MSC. Clinical management of this response may minimize this effect. Intra-articular MSC demonstrated a persistent mononuclear infiltrate for at least 60 days, the significance of which is not known. An adaptive immune response was detected for xenogeneic but not for allogeneic MSC suggesting that a second intra-articular injection of xenogeneic MSC would result in a stronger inflammatory response.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Veterinary Clinical Sciences

Grantor dc:publisher

The Ohio State University

Year dc:date

2013

Author dc:creator

• Pigott, John H.

Contributors dc:contributor

• Bertone, Alicia

• Veterinary Services
• Mesenchymal stem cell
• equine
• joint
• inflammation

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=osu1365030665

OAI identifier oai:identifier

oai:etd.ohiolink.edu:osu1365030665