Combinatorial ECM Arrays Identify Cooperative Roles for Matricellular Proteins in Enhancing the Generation of TH+ Neurons From Human Pluripotent Cells

Maqsood Ahmed; Matthew J S Owens; Enrique M Toledo; Ernest Arenas; Mark Bradley; Charles Ffrench-Constant

doi:10.3389/fcell.2021.755406

Combinatorial ECM Arrays Identify Cooperative Roles for Matricellular Proteins in Enhancing the Generation of TH+ Neurons From Human Pluripotent Cells

Front Cell Dev Biol. 2021 Dec 1:9:755406. doi: 10.3389/fcell.2021.755406. eCollection 2021.

Authors

Maqsood Ahmed¹, Matthew J S Owens², Enrique M Toledo³, Ernest Arenas³, Mark Bradley², Charles Ffrench-Constant^{1

4}

Affiliations

¹ Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
² School of Chemistry, EaStCHEM, University of Edinburgh, Edinburgh, United Kingdom.
³ Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
⁴ Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, England.

Abstract

The development of efficient cell culture strategies for the generation of dopaminergic neurons is an important goal for transplantation-based approaches to treat Parkinson's disease. To identify extracellular matrix molecules that enhance differentiation and might be used in these cell cultures we have used micro-contact printed arrays on glass slides presenting 190 combinations of 19 extracellular matrix molecules selected on the basis of their expression during embryonic development of the ventral midbrain. Using long-term neuroepithelial stem cells (Lt-NES), this approach identified a number of matricellular proteins that enhanced differentiation, with the combination of Sparc, Sparc-like (Sparc-l1) and Nell2 increasing the number of tyrosine hydroxylase+ neurons derived from Lt-NES cells and, critically for further translation, human pluripotent stem cells.

Keywords: array; dopaminergic (DA) neuron; extracellular matrix; matricellular proteins; neural stem cells; tyrosine hydroxylase.

Abstract

Grants and funding