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Neurochemical Research

, Volume 42, Issue 2, pp 415–427 | Cite as

Improved Proliferative Capacity of NP-Like Cells Derived from Human Mesenchymal Stromal Cells and Neuronal Transdifferentiation by Small Molecules

  • Alejandro Aguilera-Castrejon
  • Herminia Pasantes-Morales
  • Juan José Montesinos
  • Lorena V. Cortés-Medina
  • Marta E. Castro-Manrreza
  • Héctor Mayani
  • Gerardo Ramos-MandujanoEmail author
Original Paper

Abstract

Neural progenitors (NP), found in fetal and adult brain, differentiate into neurons potentially able to be used in cell replacement therapies. This approach however, raises technical and ethical problems which limit their potential therapeutic use. Alternately, NPs can be obtained by transdifferentiation of non-neural somatic cells evading these difficulties. Human bone marrow mesenchymal stromal cells (MSCs) are suggested to transdifferentiate into NP-like cells, which however, have a low proliferation capacity. The present study demonstrates the requisite of cell adhesion for proliferation and survival of NP-like cells and re-evaluates some neuronal features after differentiation by standard procedures. Mature neuronal markers, though, were not detected by these procedures. A chemical differentiation approach was used in this study to convert MSCs-derived NP-like cells into neurons by using a cocktail of six molecules, CHIR99021, I-BET151, RepSox, DbcAMP, forskolin and Y-27632, defined after screening combinations of 22 small molecules. Direct transdifferentiation of MSCs into neuronal cells was obtained with the small molecule cocktail, without requiring the NP-like intermediate stage.

Keywords

Mesenchymal stromal cells Neural progenitor cells Transdifferentiation Cell proliferation Neuronal reprogramming Small molecules 

Notes

Acknowledgments

This work was supported by the Dirección General de Asuntos del Personal Académico (DGAPA), Universidad Nacional Autónoma de México (UNAM) (H.P.M. and G.R.M., Grant No. IN205916). We are indebted to the National Council of Science and Technology (CONACYT) for support to J.J.M.M. (Grant No. 258205), IMSS support to J.J.M.M. (Grant No. 1311), and CONACYT Red temática células troncales y medicina regenerative (Grant No. 271609). A.A.C. acknowledge the financial support provided by the “Ayudante de Investigador Nacional Emérito” fellowship of CONACYT (Núm. Exp. 10802). We thank QFB Carlos Castellanos Barba from the flow-cytometry unit at the Instituto de Investigaciones Biomédicas for his expert technical assistance in flow cytometry protocols. We also thank Dr. Laura Ongay Larios from the molecular biology unit at the Instituto de Fisiología Celular for her assistance with qPCR.

Author Contributions

A.A.C. conception and design, collection and/or assembly of data, data analysis and interpretation, figure preparation, manuscript writing and final approval of manuscript. H.P.M. Conception and design, financial support, manuscript writing, and final approval of manuscript. L.V.C.M. collection and/or assembly of data and data analysis and interpretation. J.J.M. Provision of study material, financial support, and final approval of manuscript; M.E.C.M. Provision of study material and collection and assembly of data; H.M. Financial support and final approval of manuscript; G.R.M. conception and design, collection and/or assembly of data, data analysis and interpretation, figure preparation, financial support, manuscript writing and final approval of manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11064_2016_2086_MOESM1_ESM.pdf (320 kb)
Supplementary material 1 (PDF 319 KB)
11064_2016_2086_MOESM2_ESM.xlsx (28 kb)
Supplementary material 2 (XLSX 27 KB)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Alejandro Aguilera-Castrejon
    • 1
  • Herminia Pasantes-Morales
    • 1
  • Juan José Montesinos
    • 2
  • Lorena V. Cortés-Medina
    • 1
  • Marta E. Castro-Manrreza
    • 2
    • 4
  • Héctor Mayani
    • 3
  • Gerardo Ramos-Mandujano
    • 1
    Email author
  1. 1.División de Neurociencias, Instituto de Fisiología CelularUniversidad Nacional Autónoma de MéxicoMexico CityMexico
  2. 2.Mesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical CenterIMSSMexico CityMexico
  3. 3.Hematopoietic Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical CenterIMSSMexico CityMexico
  4. 4.CONACYT-Children Hospital of Mexico Federico GómezMexico CityMexico

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