Investigation of the immune response to autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses.

This research article focuses on understanding the immune response in horses after injecting them with different types of mesenchymal stem cells (MSC). The stem cells used were autologous (originating from the same individual), allogeneic (originating from another individual of the same species) and xenogeneic (originating from a different species). The study found that intra-articular injection of any of these stem cells can cause a persistent immune response, but the extent of the response varies based on the origin of the stem cells.

Research Methodology

• The researchers selected six five-year-old Thoroughbred mares for the study. These horses had previously been injected with 15 million genetically modified MSCs of each type into their fetlock joints.
• One group of autologous cells was further modified to enable the researchers to track their location within the synovium (joint tissues).
• To assess the horses’ responses to the injections, synovial biopsies were obtained through arthroscopy 60 days after the MSC injection. These biopsies were then subjected to gross, histologic, and molecular analyses.
• Additionally, peripheral blood mononuclear cells were isolated from each horse 120 days after the MSC injection and co-cultured with a monolayer of each MSC group in order to estimate the number of activated CD4+ lymphocytes and evaluate cytokine release upon re-exposure to MSCs.

Research Findings

• Synovial examination revealed no overt negative effects to the joint tissues or cartilage.
• It was observed that an infiltration of mononuclear cells occurred and persisted for at least 60 days after injecting MSCs. The infiltrating cells were majorly perivascular and were identified as CD3+ lymphocytes.
• A significant immune response was detected upon the re-exposure to xenogeneic MSCs, characterized by an increase in the number of CD4+ lymphocytes. However, no significant response was noted upon re-exposure to allogeneic or autologous MSCs.
• An inflammatory response was observed in cases where peripheral blood mononuclear cells had been co-cultured with each group of MSCs. However, this inflammatory response was significantly higher upon co-culturing with the xenogeneic group.

Conclusion

• Based on their observations, the researchers concluded that intra-articular MSC injection can cause a persistent immune response, evident as synovitis. However, the extent of this immune response depends on the origin of the stem cells. The allogeneic cells, in particular, did not elicit a significant immune response upon re-exposure as per the detection methods used in this study.