Frontiers in Cell and Developmental Biology (Dec 2021)

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,
  • Charles ffrench-Constant

DOI
https://doi.org/10.3389/fcell.2021.755406
Journal volume & issue
Vol. 9

Abstract

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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.

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