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

Stem Cell Research & Therapy

Zoe Hewitt¹  Harry Moore¹  Loriana Vitillo²  Ludovic Vallier²  Catherine Durance²  Austin Smith³ 

[1] The Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Western Bank, S10 2TN, Sheffield, UK;Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre; Department of Surgery, University of Cambridge, CB2 0AW, Cambridge, UK;Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre; Department of Surgery, University of Cambridge, CB2 0AW, Cambridge, UK;Living Systems Institute, University of Exeter, EX4 4QD, Exeter, UK;

关键词: Pluripotent stem cells;    hESCs;    Neural progenitors;    GMP;    Cell therapy;   

DOI  :  10.1186/s13287-020-01915-0

来源: Springer

【 摘 要 】

BackgroundA 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.MethodsWe 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.ResultsHere, 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.ConclusionsOverall, 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.

【 授权许可】

CC BY