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Research Article

Clinicopathologic findings following intra-articular injection of autologous and allogeneic placentally derived equine mesenchymal stem cells in horses

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Pages 419-430 | Received 17 May 2010, Accepted 07 Oct 2010, Published online: 25 Nov 2010
 

Abstract

Background aims. The development of an allogeneic mesenchymal stem cell (MSC) product to treat equine disorders would be useful; however, there are limited in vivo safety data for horses. We hypothesized that the injection of self (autologous) and non-self (related allogeneic or allogeneic) MSC would not elicit significant alterations in physical examination, gait or synovial fluid parameters when injected into the joints of healthy horses. Methods. Sixteen healthy horses were used in this study. Group 1 consisted of foals (n = 6), group 2 consisted of their dams (n = 5) and group 3 consisted of half-siblings (n = 5) to group 1 foals. Prior to injection, MSC were phenotyped. Placentally derived MSC were injected into contralateral joints and MSC diluent was injected into a separate joint (control). An examination, including lameness evaluation and synovial fluid analysis, was performed at 0, 24, 48 and 72 h post-injection. Results. MSC were major histocompatibility complex (MHC) I positive, MHC II negative and CD86 negative. Injection of allogeneic MSC did not elicit a systemic response. Local responses such as joint swelling or lameness were minimal and variable. Intra-articular MSC injection elicited marked inflammation within the synovial fluid (as measured by nucleated cell count, neutrophil number and total protein concentration). However, there were no significant differences between the degree and type of inflammation elicited by self and non-self-MSC. Conclusions. The healthy equine joint responds similarly to a single intra-articular injection of autologous and allogeneic MSC. This pre-clinical safety study is an important first step in the development of equine allogeneic stem cell therapies.

Acknowledgments

This project was supported in part by Thermo Genesis Corp., Rancho Cordova, CA, USA.

Financial support was also provided by the Center for Equine Health, including the Harriet Pfleger Foundation, and a gift from Mr Dick and Carolyn Randall. The authors thank Dr Jamie A. Textor, the staff of the Center for Equine Health and the staff in the William R. Pritchard Veterinary Teaching Hospital Hematology Lab, School of Veterinary Medicine, University of California, Davis, for assistance in sample collection and processing.

Disclosure of interest: the authors have no conflict of interest

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