Effect of inflammatory environment on equine bone marrow derived mesenchymal stem cells immunogenicity and immunomodulatory properties.

The research explores the response of equine bone marrow Mesenchymal stem cells (eBM-MSCs) to three inflammatory conditions. The study findings contribute to better understanding how these cells behave in inflamed joints, a knowledge that can help improve MSC-based therapies for equine joint diseases.

Background of the Study

• The study revolves around Mesenchymal stem cells (MSCs) which are known for their regenerative potential and are currently under investigation for treating equine joint diseases.
• Inflammatory environment, caused due to release of proinflammatory mediators into synovial fluid, plays a significant role in joint diseases, leading to cartilage degradation.
• The authors point out that MSCs can modulate this local immune environment either through direct or indirect interaction with immune cells.
• While proinflammatory molecules can induce MSC immunoregulatory potential, they can also increase the expression of immunogenic molecules. Hence, it is important to study the effects of an inflammatory environment on MSC immunomodulation and immunogenicity profiles to enhance cellular therapies.

Aim and Methodology of the Study

• This study primarily aims to analyse the response of eBM-MSCs to three kinds of inflammatory conditions.
• Three sets of eBM-MSCs were exposed to: 20% allogenic inflammatory synovial fluid (SF); 50 ng/ml of TNFα and IFNγ (CK50); and 20 ng/ml of TNFα and IFNγ (CK20).
• After 72 hours, the team studied the expression of immunogenic and immunomodulation-related molecules, such as cell-to-cell contact and paracrine signaling molecules.

Results of the Study

• Inflammatory conditions resulted in the upregulation of adhesion molecules’ gene expression and the downregulation of MSC migration-related genes.
• CK conditions especially resulted in the significant upregulation of several molecules, including COX-2, iNOS, IDO, and IL-6.
• All the tested conditions upregulated MHC-I gene’s expression, but MHC-II was upregulated only under CK exposure.
• No significant change was found in the expression of CD40, but its ligand CD40L downregulated in CK conditions.
• Flow cytometry provided additional support to these results showing an increase in MHC-I and MHC-II positive cells and mean fluorescence intensity (MFI) under CK50 conditions.

Conclusion Derived from the Study

• From these results, researchers concluded that the immunophenotype of eBM-MSCs changes as per the surrounding conditions.
• Study reveals that, inflammatory synovial environments did not lead to significant changes, signalling that the environment inside an inflamed joint where eBM-MSCs are typically administered might not be sufficient to activate their immunomodulatory potential.
• On the other hand, CK priming at tested doses heightened the immunoregulatory profile of eBM-MSCs and might promote therapeutic benefits.
• Even though CK priming resulted in MHC upregulation, it did not upregulate costimulatory molecule expression, thus suggesting that immunogenicity might not be increased.
• This research provides insights into the behaviour of eBM-MSCs in inflamed joints, marking an important step toward enhancing MSC-based therapies for equine joint diseases.