Neural differentiation medium for human pluripotent stem cells to model physiological glucose levels in human brain

Michal E Mor; Alexandra Harvey; Mary Familari; Mitchell St Clair-Glover; Serena Viventi; Robb U de Iongh; Fergus J Cameron; Mirella Dottori

doi:10.1016/j.brainresbull.2021.05.016

Neural differentiation medium for human pluripotent stem cells to model physiological glucose levels in human brain

Brain Res Bull. 2021 Aug:173:141-149. doi: 10.1016/j.brainresbull.2021.05.016. Epub 2021 May 19.

Authors

Michal E Mor¹, Alexandra Harvey², Mary Familari², Mitchell St Clair-Glover³, Serena Viventi⁴, Robb U de Iongh¹, Fergus J Cameron⁵, Mirella Dottori⁶

Affiliations

¹ Department of Anatomy & Physiology, University of Melbourne, Australia.
² School of BioSciences, University of Melbourne, Australia.
³ Illawarra Health and Medical Research Institute, Molecular Horizons, University of Wollongong, Australia.
⁴ The Florey Institute of Neuroscience and Mental Health, Australia.
⁵ Murdoch Children's Research Institute, The Royal Children's Hospital, Australia; Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Australia.
⁶ Department of Anatomy & Physiology, University of Melbourne, Australia; Illawarra Health and Medical Research Institute, Molecular Horizons, University of Wollongong, Australia; Department of Biomedical Engineering, University of Melbourne, Australia. Electronic address: mdottori@uow.edu.au.

PMID: 34022288
DOI: 10.1016/j.brainresbull.2021.05.016

Abstract

Cortical neurospheres (NSPs) derived from human pluripotent stem cells (hPSC), have proven to be a successful platform to investigate human brain development and neuro-related diseases. Currently, many of the standard hPSC neural differentiation media, use concentrations of glucose (approximately 17.5-25 mM) and insulin (approximately 3.2 μM) that are much greater than the physiological concentrations found in the human brain. These culture conditions make it difficult to analyse perturbations of glucose or insulin on neuronal development and differentiation. We established a new hPSC neural differentiation medium that incorporated physiological brain concentrations of glucose (2.5 mM) and significantly reduced insulin levels (0.86 μM). This medium supported hPSC neural induction and formation of cortical NSPs. The revised hPSC neural differentiation medium, may provide an improved platform to model brain development and to investigate neural differentiation signalling pathways impacted by abnormal glucose and insulin levels.

Keywords: Culture media; Glucose; Human pluripotent stem cells; Insulin; Neural differentiation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain / cytology
Brain / metabolism*
Cell Differentiation / physiology*
Culture Media
Glucose / metabolism*
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism*

Substances

Culture Media
Glucose