GMP-grade neural progenitor derivation and differentiation from clinical-grade human embryonic stem cells

A major challenge for the clinical use of human pluripotent stem cells is the development of safe, robust and controlled differentiation protocols. Adaptation of research protocols using reagents designated as research-only to those which are suitable for clinical use, often referred to as Good Manufacturing Practice (GMP) reagents, is a crucial and laborious step in the translational pipeline. However, published protocols to assist this process remain very limited. Here we present a new GMP-compliant protocol to derive long-term neuroepithelial stem cell progenitors (lt-NES), which are multipotent, bankable, and karyotypically stable. This protocol resulted in robust and reproducible differentiation of several clinical-grade embryonic stem cells, deposited in the UK Stem Cell Bank, from which we derived lt-NES. Furthermore, GMP-derived lt-NES demonstrated a high neurogenic potential while retaining the ability to be redirected to several neuronal sub-types. Overall, we report the feasibility of derivation and differentiation of clinical grade embryonic stem cell lines into lt-NES under GMP-compliant conditions. Our protocols could be used as a flexible tool to speed up translation-to-clinic of pluripotent stem cells for a variety of neurological therapies or regenerative medicine studies.