Exosomes/EVs: Late Breaking Abstract: EFFECTS OF AMNIOTIC FLUID DERIVED EXTRACELLULAR VESICLE BIOLOGIC ON T CELL PROLIFERATION AND ACTIVATION

ABSTRACT

Background & Aim: Extracellular Vesicles (EVs) isolated from single cell sources such as mesenchymal stem cells and biological fluids such as amniotic fluid have previously been found to have various effects on immune cell functions. Zofin is an acellular biologic derived from amniotic fluid and contains naturally occurring EVs. Zofin is currently under clinical investigation for COVID-19 infection and Post Acute Sequale of COVID-19. Therefore, we aimed to investigate the effects of Zofin on the lymphocyte immune response in an in vitro cell culture model. Methods, Results & Conclusion: Zofin was manufactured from fullterm amniotic fluid collected from healthy, consenting mothers during planned cesarean section. The Zofin used in these experiments contained 1.5x1011 particles/ml as quantified by Nanosight NS300. To study the immune response in vitro, PBMCs were stimulated with 5μg/ml Phytohemagglutinin (PHA) for up to 8 days. PBMCs were labeled before culture with cell trace dye to monitor changes in proliferation. Stimulated PBMCs were treated with either serum-free media (vehicle) or different concentrations of Zofin (10% and 20%). 4 days following PHA stimulation, Zofin suppressed PHA-induced T cell proliferation in a dose-dependent manner. 8 days following PHA stimulation there were higher rates of proliferation, Zofin maintained suppressed proliferation at 20% concentrations. In the same cell culture model, treatment with Zofin attenuated a PHA-induced increase in T cell activation as observed by a reduction in expression of activation markers. Overall, this data demonstrates that Zofin has an effect on the immune response of T cells and suggests amniotic fluid derived EVs could be used as an immunotherapeutic tool