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

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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.
Original languageEnglish
Article number755406
JournalFrontiers in Cell and Developmental Biology
Volume9
DOIs
Publication statusPublished - 1 Dec 2021

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