Dynamics of mesenchymal stromal cell potency during ex vivo bioreactor therapy

Aneesha Doshi
2022
Mesenchymal stromal cells have become a candidate for cell therapy due to potent immunomodulatory properties exhibited in their secretome. However, they have shown limited clinical success due to issues of dosing and persistence when administered in vivo. A scalable hollow fiber bioreactor device has been created to deliver MSC therapeutics in an ex vivo manner. The potency and behavior of MSCs in this bioreactor can be explored via a dynamic perfusion system, collecting the MSC secretome in
more » ... iodic fractions and comparing the MSC behavior at different time points and in response to a variety of factors. Herein, a study was designed to determine the dynamic potency of the MSC secretome using this device and characterize their secreted factors when cocultured with immune cells. Three studies were designed to characterize the dynamic baseline MSC behavior, determine how MSCs behave in a model of an inflamed patient, and understand the effect of prelicensing MSCs on their dynamic potency. Results indicate an ideal dosing time of 24 hours and significant benefits when prelicensing MSCs used in the device. Ultimately, this research can be translated clinically to maximize the potency of the MSC therapy, minimize side effects, and allow greater control for the duration of the ex vivo bioreactor therapy.
doi:10.7282/t3-66d1-ra75 fatcat:nxpqedknyfalfag4glpfjerfku