Chemically induced specification of retinal ganglion cells from human embryonic and induced pluripotent stem cells.
Stem Cells Transl Med
; 3(4): 424-32, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24493857
ABSTRACT
The loss of retinal ganglion cells (RGCs) is the primary pathological change for many retinal degenerative diseases. Although there is currently no effective treatment for this group of diseases, cell transplantation to replace lost RGCs holds great potential. However, for the development of cell replacement therapy, better understanding of the molecular details involved in differentiating stem cells into RGCs is essential. In this study, a novel, stepwise chemical protocol is described for the differentiation of human embryonic stem cells and induced pluripotent stem cells into functional RGCs. Briefly, stem cells were differentiated into neural rosettes, which were then cultured with the Notch inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT). The expression of neural and RGC markers (BRN3A, BRN3B, ATOH7/Math5, γ-synuclein, Islet-1, and THY-1) was examined. Approximately 30% of the cell population obtained expressed the neuronal marker TUJ1 as well the RGC markers. Moreover, the differentiated RGCs generated action potentials and exhibited both spontaneous and evoked excitatory postsynaptic currents, indicating that functional and mature RGCs were generated. In combination, these data demonstrate that a single chemical (DAPT) can induce PAX6/RX-positive stem cells to undergo differentiation into functional RGCs.
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Base de dados:
MEDLINE
Assunto principal:
Células Ganglionares da Retina
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Antígenos de Diferenciação
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Diferenciação Celular
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Dipeptídeos
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Células-Tronco Embrionárias
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Células-Tronco Pluripotentes Induzidas
Tipo de estudo:
Guideline
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article