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Stem Cell Reports. 2014 Dec 9;3(6):1118-31. doi: 10.1016/j.stemcr.2014.10.008. Epub 2014 Nov 13.

Fast and efficient neural conversion of human hematopoietic cells.

Author information

1
Josep Carreras Leukemia Research Institute, Cell Therapy Program of the University of Barcelona, Barcelona 08036, Spain.
2
Josep Carreras Leukemia Research Institute, Cell Therapy Program of the University of Barcelona, Barcelona 08036, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain.
3
Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa 48940, Spain.
4
Department of Cell Biology, Immunology and Neurosciences, Faculty of Medicine, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona 08036, Spain; Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona 08036, Spain.
5
Laboratory of Stem Cells and Neural Repair, Inbiomed, San Sebastian 20009, Spain.
6
Cell Reprogramming and Differentiation Platform, Inbiomed, San Sebastian 20009, Spain.
7
Laboratory of Stem Cells and Neural Repair, Inbiomed, San Sebastian 20009, Spain; Cell Reprogramming and Differentiation Platform, Inbiomed, San Sebastian 20009, Spain.
8
Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
9
Laboratory of Stem Cells and Neural Repair, Inbiomed, San Sebastian 20009, Spain. Electronic address: rpernaute@inbiomed.org.
10
Josep Carreras Leukemia Research Institute, Cell Therapy Program of the University of Barcelona, Barcelona 08036, Spain. Electronic address: agiorgetti@carrerasresearch.org.

Abstract

Neurons obtained directly from human somatic cells hold great promise for disease modeling and drug screening. Available protocols rely on overexpression of transcription factors using integrative vectors and are often slow, complex, and inefficient. We report a fast and efficient approach for generating induced neural cells (iNCs) directly from human hematopoietic cells using Sendai virus. Upon SOX2 and c-MYC expression, CD133-positive cord blood cells rapidly adopt a neuroepithelial morphology and exhibit high expansion capacity. Under defined neurogenic culture conditions, they express mature neuronal markers and fire spontaneous action potentials that can be modulated with neurotransmitters. SOX2 and c-MYC are also sufficient to convert peripheral blood mononuclear cells into iNCs. However, the conversion process is less efficient and resulting iNCs have limited expansion capacity and electrophysiological activity upon differentiation. Our study demonstrates rapid and efficient generation of iNCs from hematopoietic cells while underscoring the impact of target cells on conversion efficiency.

PMID:
25458894
PMCID:
PMC4264063
DOI:
10.1016/j.stemcr.2014.10.008
[Indexed for MEDLINE]
Free PMC Article

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