UOH – University of Ottawa Heart Institute Academic Medical Organization
UOH-21-003 – Stem cell solutions for COVID-19 related acute respiratory distress syndrome
Although 90% of infections with the novel coronavirus 2 (COVID-19) are mild, many patients progress to acute respiratory distress syndrome (ARDS) which carries a high risk of mortality. Given that this dysregulated immune response plays a key role in the pathology of COVID-19, several clinical trials are underway to evaluate the effect of immunomodulatory cell therapy on disease progression. However, little is known about the effect of ARDS associated pro-inflammatory mediators on transplanted stem cell function and survival, and any deleterious effects could undermine therapeutic efficacy. As such, we assessed the impact of inflammatory cytokines on the viability and paracrine profile (extracellular vesicles) of bone marrow derived mesenchymal stromal cells, heart-derived cells, and umbilical cord derived mesenchymal stromal cells. All cell products were manufactured to established clinical release standards by an accredited clinical cell manufacturing facility. Using a survey of the clinical literature, we identified 6 cytotoxic cytokines implicated in the progression of COVID-19 ARDS. Flow cytometry revealed the presence of receptors for all cytokines but IL-6, which was subsequently excluded from further experimentation. Despite this widespread expression, exposure of each cell type to individual cytokines at doses 10-fold greater than observed clinically or in combination at doses associated with severe ARDS did not alter cell viability or extracellular vesicle character/production in any of the 3 cell products. Conclusion: The paracrine production and viability of the three leading cell products under clinical evaluation for the treatment of severe COVID-19 ARDS are not altered by inflammatory mediators implicated in disease progression.
Prevention and Treatment
Primary Project Lead for Contact