Modeling Human Mesenchymal Stem Cell Expansion in Vertical Wheel Bioreactors Using Lactate Production Rate in Regenerative Medicine Biomanufacturing

Stem cells are critical components of regenerative medicine therapy. However, the therapy will require millions to billions of therapeutic stem cells. To address the need, we have recently cultured stem cells in 3D microgels and used them as a vehicle for cell expansion within a low shear stress rotating wheel type bioreactor within a 500ml volumetric setting. This study specifically highlights the cell encapsulation in microbead process, harvesting and operation of microbeads within a dynamic bioreactor environment. We have specifically encapsulated stem cells (human adipose derived) into microbeads prepared from alginate hydrogels via an electrostatic jetting process. This study highlights the effect of fabrication process parameters on end-point biological quality measures such as stem cell count and viability. We were able to maintain a >80% viability during the 21 day static culture period. We have also measured the concentration of metabolites produced during the expansion, specifically lactate production measured during specific time points within culture inside the rotating wheel bioreactor Future work will need to address predicting yields in higher volume settings, efficiency of harvest and a more detailed description of the hydrodynamics affecting stem cell growth.