SBIR Phase I: Hypothalamus Stem Cell Exosomes for Treatment of COVID-19 (COVID-19)

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to create a novel type of therapeutic using cutting-edge technology and adult stem cells. This therapeutic may be used in hospitals to treat patients with severe COVID-19 infection; the proposed drugs would be made from the cells of healthy brains and have the capability to correct an aberrant immune response in sick people. This can potentially be used for other neurodegenerative diseases as well as for other drug discovery research. This Small Business Innovative Research (SBIR) Phase I project addresses the urgent need for development of drugs to modulate the immune response to prevent escalation of COVID-19 to acute respiratory distress syndrome (ARDS). The hypothalamus is crucial to secretion of cortisol and other modulators that dampen the immune response following activation. This project will test whether exosome-based therapeutics produced from hypothalamus stem cells can abate the cytokine storm that causes ARDS in COVID-19 patients. Technical tasks include: 1) engineer pluripotent cells to produce exosomes with enhanced neuronal specificity by transducing cells with the XStamp-BHP1 and XStamp-NCAM lentiviral vectors; 2) grow pluripotent cells at scale using the mTesr3D system; 3) induce cells to differentiate into hypothalamus stem cells; 4) collect exosomes. The technical milestone is to engineer exosomes with at least a 70% enhanced neuronal specificity and to produce highly concentrated hypothalamus stem cell exosome particles. These engineered human hypothalamus stem cell exosomes can be used to dampen the cytokine storm in a mouse model of LPS-induced ARDS. This proposal establishes the feasibility of using hypothalamus stem cells as therapeutic candidates for treatment of ARDS in COVID-19. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.