Modeling the selective growth advantage of genetically variant human pluripotent stem cells to identify opportunities...

The appearance of genetically variant populations in human pluripotent stem cell (hPSC) cultures represents a concern for research and clinical applications. Genetic variations may alter hPSC differentiation potential or cause phenotype variation in differentiated cells. Further, variants may have properties such as proliferative rate, or response to the culture environment, that differ from wild-type cells. As such, understanding the behavior of these variants in culture, and any potential operational impact on manufacturing processes, will be necessary to control quality of putative hPSC-based products that include a proportion of variant threshold in their quality specification.

Here we show a computational model that mathematically describes the growth dynamics between commonly occurring genetically variant hPSCs and their counterpart wild-type cells in culture.

We show that our model is capable of representing the growth behaviors of both wild-type and variant hPSCs in individual and co-culture systems.

This representation allows us to identify three critical process parameters that drive critical quality attributes when genetically variant cells are present within the system: total culture density, proportion of variant cells within the culture system and variant cell overgrowth. Lastly, we used our model to predict how the variability of these parameters affects the prevalence of both populations in culture.