A tool for rapid development of clinical-grade protocols for dopaminergic neuronal differentiation of Parkinson’s Disease patient-derived iPSCs

This project has allowed deployment of the Cell Therapy Development Engine, Scaled Biolabs’ platform for enabling accelerated discovery and optimization of stem cell differentiation into desired lineages, and specifically for the derivation of dopaminergic neurons as a curative cell therapy for Parkinson’s disease. The platform incorporates wetware - highly parallel microfluidic cell culture under combinatorial conditions; hardware - an automation system capable of remotely executing stem cell differentiations in the microfluidic chip; and software - an image and data analysis pipeline allowing single-cell level enumeration of subpopulations derived from stem cells. Applied to the challenge of robust generation of dopaminergic neurons, the platform facilitated reliable generation of progenitor cells at purities reliably exceeding 80% across 8 cell lines, and with process economics representing cost savings of up to 60% versus current protocols, as well as simplification of the process components. Efficient conversion of these progenitors into high-purity tyrosine hydroxylase (TH)-positive dopaminergic neurons remains a key challenge prior to transplantation, with cell line variability still the major impeding factor. The landscape of medium compositions evaluated in this project provides data on ineffective approaches, as well as molecules that show signs of enhancing conversion. The engine remains active in continuing to optimize end stage conversion to target cell phenotypes.