Researchers advance precision bioengineering of human pluripotent stem cells

New research is enhancing the precision and efficiency of human pluripotent stem cell (hPSC) engineering, addressing key limitations in regenerative medicine and immunotherapy.

One study utilized parallel genome-scale CRISPR-Cas9 loss-of-function screens to distinguish between genes responsible for stem cell fitness and those regulating pluripotent identity. This research identified specific mitochondrial, metabolic, and chromatin regulators that control these distinct aspects of self-renewal, providing a framework for categorizing gene functions in stem cell research.

Complementary work at the University of Ottawa has introduced a modular bioengineering platform designed to overcome challenges such as slow differentiation kinetics and transgene silencing. By using a multiplexed CRISPR activation system, researchers successfully accelerated the differentiation of human-induced pluripotent stem cells (hiPSCs) into brain endothelial-like cells, reducing timelines by 61%. Additionally, the development of a site-specific engineering platform targeting genomic safe harbours allows for more stable and predictable transgene expression during lineage commitment.