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Preliminary evaluation of equine umbilical cord blood mesenchymal stromal cells as treatment of synovitis

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Title: Preliminary evaluation of equine umbilical cord blood mesenchymal stromal cells as treatment of synovitis
Author: Williams, Lynn
Department: Department of Biomedical Sciences
Program: Animal and Poultry Science
Advisor: Koch, ThomasKoenig, Judith
Abstract: Joint injury is the leading cause of premature retirement of athletic horses and is associated with significant financial losses to the equine industry. As current therapies for joint injury are only palliative in nature, there is a clinical need for therapies that alter the progression of joint disease. Despite a lack of evidence, mesenchymal stromal cell (MSC) therapy is being pursued for treatment of joint disease in the hope that the MSC will alter disease progression. The twofold purpose of this thesis is to evaluate the effect of allogeneic MSC therapy as treatment for synovitis and to evaluate strategies for improving MSC delivery methods in order to maintain optimal MSC viability. Intra-articular injection of allogeneic equine umbilical cord blood (CB) MSC with confirmed in vitro lymphocyte suppressive properties into normal joints resulted in a mild self-limiting inflammatory reaction. Co-injection of lipopolysaccharide (LPS) and allogeneic CB-MSC significantly decreased the cellular response associated with the initial inflammatory insult while inducing mild self-limiting inflammation. We also determined that cryogenic storage did not affect the in vitro lymphocyte suppressive capacity of umbilical cord blood (CB) derived MSC cultures and that injection through various diameter hypodermic needles did not decrease CB or bone marrow (BM) derived MSC viability in vitro. Aspiration, however, of BM and CB-MSC did significantly decrease MSC viability indicating care is needed where MSC suspensions are subject to negative pressure. The intravenous safety profile of two carrier solutions proposed for the final product formulation for excipient use of CB-MSC was tested in vivo. Excipient use of HypoThermosol® FRS or Cryostor® alone or in combination with pooled allogeneic CB-MSC resulted in no change in outcome parameters of physical exam, CBC, biochemistry profile, or coagulation profile in healthy ponies. Interestingly, an increase in CD4+ and CD8+ lymphocyte populations were observed 168h post CB-MSC injection indicating a possible allogeneic immune response. This is the first report of a quantitative effect of IA CB-MSC therapy in a randomized blinded experimental study. Further study is needed to evaluate IA MSC therapy in chronic inflammatory models or naturally occurring osteoarthritis. Questions of interest include evaluating dose, timing of treatment, effect of multiple injections, and conditions responsive to MSC treatment in horses.
Date: 2015-06

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