Dispersible and Dissolvable Porous Microcarrier Tablets Enable Efficient Large-Scale Human Mesenchymal Stem Cell Expansion

Human mesenchymal stem cells (hMSCs) have wide applications in regenerative medicine but their clinical translation is largely hindered by limited production capacity of current cell expansion regime. This study utilizes a novel dispersible and dissolvable porous microcarrier tablet, 3D TableTrix™, in stirred bioreactor to demonstrate a scalable expansion protocol for industrial manufacturing of hMSCs. The 3D TableTrix is a ready-to-use tablet that disperses into 10s of 1000s porous microcarriers upon contact with culture media, eliminating the need to prepare microcarriers before cell seeding, hence simplifying operation process. We demonstrate over 500 times expansion of adipose-derived hMSCs using serum-free culture medium in 11 days with bead-to-bead transfer for a partial scale-up from laboratory-scale spinner flasks to a 1-L bioreactor system. A final yield of 1.05 ± 0.11 × 10 9 hMSCs was achieved, and yield of over 3 × 10 9 with an overall expansion factor of 1530 could theoretically be realized with full scale-up. Cells were harvested by dissolving microcarriers with 98.6% ± 0.1% recovery rate. Cells retained their immunophenotypic characteristics, trilineage differentiation potential, and genome stability with low indications of senescence phenotype. This study illuminates the potential of industrializing clinical-grade hMSC production using 3D TableTrix microcarrier tablets and stirred tank bioreactors. Impact statement The 3D TableTrix™ is a newly available microcarrier ingeniously designed as dispersible and dissolvable porous microcarrier tablets for human mesenchymal stem cell (hMSC) expansion. This eliminates the need of tedious preparation work usually required for microcarriers and its dissolvable nature allows for high cell recovery rate of 98.6% ± 0.1%. Over 500 times expansion of adipose-derived mesenchymal stem cells in serum-free culture media using a 1-L bioreactor system demonstrates its tremendous potential for industrial production of hMSCs.