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


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Authors
Durance, Catherine 
Hewitt, Zoe 
Moore, Harry 
Smith, Austin 
Abstract

Abstract: Background: 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. Methods: We adapted research-grade protocols for the derivation and differentiation of long-term neuroepithelial stem cell progenitors (lt-NES) to GMP-grade reagents and factors suitable for clinical applications. We screened the robustness of the protocol with six clinical-grade hESC lines deposited in the UK Stem Cell Bank. Results: Here, we present a new GMP-compliant protocol to derive lt-NES, which are multipotent, bankable and karyotypically stable. This protocol resulted in robust and reproducible differentiation of several clinical-grade embryonic stem cells 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. Conclusions: 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.

Description

Funder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265


Funder: Biotechnology and Biological Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000268


Funder: Engineering and Physical Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000266

Keywords
Research, Pluripotent stem cells, hESCs, Neural progenitors, GMP, Cell therapy
Journal Title
Stem Cell Research & Therapy
Conference Name
Journal ISSN
1757-6512
Volume Title
11
Publisher
BioMed Central