Ten-eleven translocation methylcytosine dioxygenase 3-loaded microspheres penetrate neurons in vitro causing active demethylation and neurite outgrowth.
J Tissue Eng Regen Med
; 15(5): 463-474, 2021 05.
Article
en En
| MEDLINE
| ID: mdl-33735542
ABSTRACT
Epigenetic processes, such as DNA methylation and other chromatin modifications, are believed to be largely responsible for establishing a reduced capacity for growth in the mature nervous system. Ten-eleven translocation methylcytosine dioxygenase 3 (Tet3)-, a member of the Tet gene family, plays a crucial role in promoting injury-induced DNA demethylation and expression of regeneration-associated genes in the peripheral nervous system. Here, we encapsulate Tet3 protein within a clinically tolerated poly(lactide-co-glycolide) microsphere system. Next, we show that Tet3-loaded microspheres are internalized into mHippoE-18 embryonic hippocampal cells. We compare the outgrowth potential of Tet3 microspheres with that of commonly used nerve growth factor (NGF)-loaded microspheres in an in vitro injury model. Tet3-containing microspheres increased levels of nuclear 5-hydroxymethylcytosine indicating active demethylation and outperformed NGF-containing microspheres in measures of neurite outgrowth. Our results suggest that encapsulated demethylases may represent a novel avenue to treat nerve injuries.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dioxigenasas
/
Proyección Neuronal
/
Desmetilación del ADN
/
Microesferas
/
Neuronas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Tissue Eng Regen Med
Asunto de la revista:
BIOTECNOLOGIA
/
HISTOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Polonia