Chemical Reprogramming of Somatic Cells in Neural Direction: Myth or Reality?

  • E. M. SamoilovaEmail author
  • V. A. Revkova
  • O. I. Brovkina
  • V. A. Kalsin
  • P. A. Melnikov
  • M. A. Konoplyannikov
  • K. R. Galimov
  • A. G. Nikitin
  • A. V. Troitskiy
  • V. P. Baklaushev

In in vitro experiments on cultures of human multipotent stem cells from the human bone

arrow and dental pulp, we studied direct reprogramming towards neuro-glial lineage cells using a cocktail of small molecules. Reprogramming by the previously published protocol (with a cocktail containing β-mercaptoethanol, LIF, VPA, CHIR99021, and RepSox) and by the optimized protocol (VPA, RG108, А83-01, dorsomorphin, thiazovivin, CHIR99021, forskolin, and Isx9) allows obtaining cells with immunophenotypic and genetic signs of neural stem cells. However, neither the former, nor the optimized protocols allowed preparing neural progenitors capable of adequate terminal differentiation from both bone marrow-derived mesenchymal stem cells and nestin-positive neural crest-derived mesenchymal stem cells. Real-time PCR demonstrated the expression of some neurogenesis markers, but neural stem cell-specific expression pattern was not observed. The findings lead us to a conclusion that reprogramming with small molecules without additional factors modifying gene expression does not allow reproducible production of human neural stem cell-like progenitors that can be used as the source of neural tissue for the regenerative therapy.

Key Words

chemical reprogramming small molecules CHIR99021 Isx9 neural stem cells 


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • E. M. Samoilova
    • 1
    Email author
  • V. A. Revkova
    • 1
  • O. I. Brovkina
    • 1
  • V. A. Kalsin
    • 1
  • P. A. Melnikov
    • 1
    • 2
  • M. A. Konoplyannikov
    • 1
    • 3
  • K. R. Galimov
    • 1
  • A. G. Nikitin
    • 1
  • A. V. Troitskiy
    • 1
  • V. P. Baklaushev
    • 1
  1. 1.Federal Research Clinical Center of Specialized Medical Care, Federal Medical-Biological Agency of RussiaMoscowRussia
  2. 2.Department of Fundamental and Applied Neurobiology, V. P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Ministry of Health of the Russian FederationMoscowRussia
  3. 3.Institute of Regenerative Medicine, I. M. Sechenov First Moscow State Medical University (Sechenov University)MoscowRussia

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