High-precision reprogramming of adult somatic cells into induced pluripotent stem cells via spatial electroporation

Human induced pluripotent stem cells (hiPSCs) are a vital resource for fundamental research, cell therapy, drug discovery, tissue engineering, and regenerative medicine. They are generated by genetically reprogramming somatic cells – such as fibroblasts or peripheral blood mononuclear cells (PBMCs) – using Yamanaka factors or alternative agents like microRNAs and small molecules. Common methods for hiPSC generation include viral gene transduction (e.g., retroviral or lentiviral vectors) and chemical induction. However, the process remains slow (typically 3 – 4 weeks) and inefficient (with reprogramming efficiencies below 0.1%), largely due to the uncontrolled delivery of reprogramming factors into cells. To address this challenge, technologies that enable precise control over the reprogramming process are in high demand.

This PhD project will investigate the use of imec’s high-definition microelectrode array (MEA) platform for on-chip hiPSC generation via spatial electroporation, using commercially available reprogramming vectors. The primary goal is to optimize electroporation parameters for efficient hiPSC induction, compare different delivery modes of reprogramming factors, and establish protocols for downstream enrichment (e.g., via antibiotic selection, microelectrocution, or chemical methods), maintenance, harvesting, expansion, and quality control.