Improved Proliferative Capacity of NP-Like Cells Derived from Human Mesenchymal Stromal Cells and Neuronal Transdifferentiation by Small Molecules.
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.
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510, Mexico City, DF, Mexico.
Alejandro
A
Aguilera-Castrejon
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510, Mexico City, DF, Mexico.
Herminia
H
Pasantes-Morales
Mesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City, Mexico.
Juan José
JJ
Montesinos
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510, Mexico City, DF, Mexico.
Lorena V
LV
Cortés-Medina
Mesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City, Mexico.|CONACYT-Children Hospital of Mexico Federico Gómez, Mexico City, Mexico.
Marta E
ME
Castro-Manrreza
Hematopoietic Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City, Mexico.
Héctor
H
Mayani
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510, Mexico City, DF, Mexico. gramos@ifc.unam.mx.
Gerardo
http://orcid.org/0000-0002-5019-4291
G
Ramos-Mandujano
D000293:Adolescent; D000328:Adult; D000577:Amides / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D054338:Cell Transdifferentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005576:Colforsin / Q000008:administration & dosage; D004338:Drug Combinations; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000008:administration & dosage; D055815:Young Adult
D000577:Amides; D004338:Drug Combinations; C568713:GSK1210151A; D006576:Heterocyclic Compounds, 4 or More Rings; D011725:Pyridines; C108830:Y 27632; D005576:Colforsin
Cell proliferation; Mesenchymal stromal cells; Neural progenitor cells; Neuronal reprogramming; Small molecules; Transdifferentiation