Highly efficient neural conversion of human pluripotent stem cells in adherent and animal-free conditions

Neural differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can produce a valuable and robust source of human neural cell subtypes, holding great promise for the study of neurogenesis and development, and for treating neurological diseases. However, curre...

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Detalhes bibliográficos
Autores: Lukovic, Dunja, Díez Lloret, Andrea, Stojkovic, Petra, Rodríguez Martínez, Daniel, Rodríguez Jiménez, Francisco Javier, González Rodríguez, P., López Barneo, José, Moreno Manzano, Victoria, Stojkovic, Miodrag, Bhattacharya, Shomi S., Erceg, Slaven
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2017
País:España
Recursos:Universidad de Sevilla (US)
Repositório:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/81101
Acesso em linha:https://hdl.handle.net/11441/81101
https://doi.org/10.1002/sctm.16-0371
Access Level:Acceso aberto
Palavra-chave:Cellular therapy
Clinical translation
Differentiation
Embryonic stem cells
Induced pluripotent stem cells
Neural differentiation
Pluripotent stem cells
Descrição
Resumo:Neural differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can produce a valuable and robust source of human neural cell subtypes, holding great promise for the study of neurogenesis and development, and for treating neurological diseases. However, current hESCs and hiPSCs neural differentiation protocols require either animal factors or embryoid body formation, which decreases efficiency and yield, and strongly limits medical applications. Here we develop a simple, animal-free protocol for neural conversion of both hESCs and hiPSCs in adherent culture conditions. A simple medium formula including insulin induces the direct conversion of >98% of hESCs and hiPSCs into expandable, transplantable, and functional neural progenitors with neural rosette characteristics. Further differentiation of neural progenitors into dopaminergic and spinal motoneurons as well as astrocytes and oligodendrocytes indicates that these neural progenitors retain responsiveness to instructive cues revealing the robust applicability of the protocol in the treatment of different neurodegenerative diseases. The fact that this protocol includes animal-free medium and human extracellular matrix components avoiding embryoid bodies makes this protocol suitable for the use in clinic.