254 - Comparing the impact of 3D bioreactor and 2D culture system on immunomodulation potency of Warton's jelly derived-MSC

Abstract

Human mesenchymal stem cells (hMSCs) are attractive cell therapy products (CTP) to treat various immune-related indications due to their broad immunomodulation capacities. The concept of “off-the-shelf” universal hMSC products for unmet and urgent clinical uses is currently focused and developed. Therefore, the large-scale three-dimensional (3D) hMSC manufacturing technology utilizing stirred-tank bioreactors accompanied with microcarrier culture system had been investigated. We have set-up the quantitative immunomodulation potency assay as MSC product release criteria, including a co-culture system of human T cell line and MSC, as well as surrogate potency markers IDO-1 and PD-L1. In this study, we explored whether a 2 L-scale 3D stirred-tank bioreactor/microcarrier culture system altered the immunomodulation potency of human Warton's jelly derived-mesenchymal stem cells (WJ-MSC) under both the basal and licensed state. Our data revealed that 3D culture system enhanced endogenous IDO-1 mRNA expression and immunomodulation potency of basal state of WJ-MSC, compared to 2D counterpart. IDO-1 and PD-L1 mRNA expression, as well as immunomodulation potency of licensed state of 3D-cultured WJ-MSC was further activated compared to the basal state. Upon post-thawing of pre-licensed 3D-cultured WJ-MSC, activated immunomodulation potency was still maintained. Based on these results, we demonstrated that WJ-MSC cultivation on microcarriers in 3D bioreactor system exhibited superior immunomodulation potency than 2D culture system. This is a promising strategy for large-scale manufacturing and commercializing off-the-shelf MSC products for treating immune-related indications.