Graduate Student Keck Grad. Inst. Tustin, California, United States
Introduction/Rationale: Presently, no effective and curative treatments exist for autoimmune diseases such as multiple sclerosis (MS). Autologous mesenchymal stem cells (MSCs) have been implicated as a curative treatment of MS, however adverse side effects remain. The mechanism of this treatment requires broad immunosuppression, causing opportunistic infections that could be potentially fatal to the patient. MSC-derived exosomes reduce the risk of opportunistic infection and present a more targeted modulation of immunological properties through natural transfer of biomolecules. These exosomes are capable of precise targeting of T-helper cells, allowing for efficient regulation of T-cell signaling and activation, which are implicated in the pathogenesis of MS. Jurkat T cells provide a reproducible in vitro model of T cell receptor-mediated signaling and therefore model the regulation of T-helper cells. No studies have yet characterized the effects of MSC-derived exosomes on Jurkat T cells; this work will fill this gap in knowledge.
Methods: The assessment of Jurkat T cell activation, proliferation, and survival was performed with flow cytometry analysis of activation markers, CSFE labeling for proliferation, and Annexin V staining for apoptosis at various time points following treatment with graded concentration of MSC-derived exosomes. Statistical analysis completed via Student’ s T-test; significance of p < 0.05.
Results: It is expected that MSC-derived exosomes will attenuate Jurkat T cell activation and proliferation through suppression of inflammatory signaling pathways, while maintaining or modestly enhancing cell survival. Outcomes agree with the immunomodulatory properties previously attributed to MSC-derived exosomes and support their potential as targeted, low-toxicity modulators of T-cell function.
Conclusion: Future studies should model these effects in primary mouse T cells under differentiation conditions to show that MSC-derived exosomes modulate effector T-cell subsets in physiologically relevant systems.
