A Spatiotemporal Microenvironment Model to Improve Design of a Three-Dimensional Bioreactor for Red Cell Production.

Cellular microenvironments provide stimuli, including paracrine and autocrine growth factors and physicochemical cues, which support efficient cell production unmatched by current biomanufacturing platforms. While three-dimensional (3D) culture systems aim to recapitulate niche architecture and function of the target tissue/organ, they are limited in accessing spatiotemporal information to evaluate and optimize cell/tissue process development. Herein, a mathematical modeling framework is parameterized by single-cell phenotypic imaging and multiplexed biochemical assays to simulate the nonuniform tissue distribution of nutrients/metabolites and growth factors in cell niche environments.