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Clinicopathologic findings following intra-articular injection of autologous and allogeneic placentally derived equine mesenchymal stem cells in horses.
Abstract: 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.
Publication Date: 2010-11-25 PubMed ID: 21105841DOI: 10.3109/14653249.2010.536213Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study investigates the safety and effects of injecting both autologous (self-derived) and allogeneic (from another individual) stem cells obtained from the placenta into the joints of healthy horses, revealing that both types of cells do not cause significant adverse responses or alterations.
Introduction and Hypothesis
- The study is premised on the need to develop a product from allogeneic mesenchymal stem cells (MSC) to treat equine disorders. The researchers identified the scarcity of safety data on this topic for horses since most of the existing research focuses more on autologous stem cell therapy.
- The main hypothesis was that the injection of both autologous and allogeneic MSC into the joints of healthy horses would not cause significant alterations in the physical examination, gait, or synovial fluid parameters (fluid found in the cavities of joints).
Methodology
- Sixteen healthy horses were involved in the experiment categorized into three groups: foals, their dams, and half-siblings to the foals.
- The experiment involved injecting placentally derived MSC into opposite joints while a control group had an MSC diluent injected into a separate joint.
- The researchers then performed detailed examinations, including lameness evaluation and synovial fluid analysis, at various time intervals post-injection (immediately, and then 24, 48 and 72 hours post-injection).
- Prior to injection, the MSCs were phenotyped (identified based on their physical and biological properties).
Results
- Results showed the MSC were positive for major histocompatibility complex (MHC) I, a group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances. They were negative for MHC II and CD86.
- No systemic reaction was caused by the injection of allogeneic MSC.
- Local responses included minimal and variable joint swelling or lameness.
- Inflammation was evident in the synovial fluid following the intra-articular MSC injection, gauged by the nucleated cell count, neutrophil number, and total protein concentration. However, the degree and type of inflammation experienced showed no significant differences between the self and non-self-MSC injections.
Conclusion
- The study concludes that the healthy equine joint responds similarly to a single intra-articular injection of both autologous and allogeneic MSC.
- This pre-clinical safety study represents a crucial first step in the development of equine allogeneic stem cell therapies, demonstrating the potential for effective and safe use of allogeneic MSC in equine treatment.
Cite This Article
APA
Carrade DD, Owens SD, Galuppo LD, Vidal MA, Ferraro GL, Librach F, Buerchler S, Friedman MS, Walker NJ, Borjesson DL.
(2010).
Clinicopathologic findings following intra-articular injection of autologous and allogeneic placentally derived equine mesenchymal stem cells in horses.
Cytotherapy, 13(4), 419-430.
https://doi.org/10.3109/14653249.2010.536213 Publication
Researcher Affiliations
- Department of Pathology, Microbiology and Immunology, University of California, Davis, California 95616, USA.
MeSH Terms
- Animals
- B7-2 Antigen / metabolism
- Female
- Histocompatibility Antigens Class I / metabolism
- Histocompatibility Antigens Class II / metabolism
- Horses
- Injections, Intra-Articular
- Mesenchymal Stem Cell Transplantation
- Placenta / cytology
- Pregnancy
- Synovial Fluid / chemistry
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