Teratogenic potential in cultures optimized for oligodendrocyte development from mouse embryonic stem cells

Stem Cells and Development
Dorota SadowskiRandall D McKinnon

Abstract

We describe a rapid and efficient 5-step program of defined factors for the genesis of brain myelin-forming oligodendrocytes (OLs) from embryonic stem cells (ESCs). The OLs emerge on the same time frame in vitro as seen in vivo. Factors promoting neural induction (retinoids, noggin) are required, while exogenous Sonic hedgehog is not. In contrast we were unable to generate OLs by trans-differentiation of ethically neutral mesenchymal stem cells, indicating a requirement for cis-differentiation via neural ectoderm for OL genesis. In the ESC-derived cultures, our optimized protocol generated a mixed population with 49% O4(+), Olig2(+) OL lineage cells. These cultures also retained pluripotential markers including Oct4, and an analysis of embryoid body formation in vitro, and allogeneic grafts in vivo, revealed that the ESC-derived cultures also retained teratogenic cells. The frequency of embryoid body formation from terminal differentiated OL cultures was 0.001%, 100-fold lower than that from ESCs. Our results provide the first quantitative measurement of teratogenicity in ESC-derived, exhaustively differentiated allogeneic grafts, and demonstrate the unequivocal need to purify ESC-derived cells in order to generate a safe popul...Continue Reading

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Citations

Apr 30, 2013·Stem Cells and Development·Walaa F AlsanieSteven Petratos
Nov 26, 2011·The International Journal of Neuroscience·Gholam Reza KakaHadi Kazemi
Mar 26, 2014·Expert Opinion on Biological Therapy·Vidyasagar Devaprasad DedeepiyaSamuel J K Abraham
Nov 26, 2015·Neural Regeneration Research·Danju Tso, Randall D McKinnon
Jul 12, 2012·Oncology Letters·Manabu TakamatsuAkira Hara
Jan 1, 2013·Brain Sciences·Alyx T Guarino, Randall D McKinnon

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Methods Mentioned

BETA
PCR
electrophoresis
flow cytometry
genetic modification

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