Overexpression of polysialylated neural cell adhesion molecule improves the migration capacity of induced pluripotent stem cell-derived oligodendrocyte precursors.
Stem Cells Transl Med
; 3(9): 1100-9, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-25069776
ABSTRACT
Cell replacement therapy aiming at the compensation of lost oligodendrocytes and restoration of myelination in acquired or congenital demyelination disorders has gained considerable interest since the discovery of induced pluripotent stem cells (iPSCs). Patient-derived iPSCs provide an inexhaustible source for transplantable autologous oligodendrocyte precursors (OPCs). The first transplantation studies in animal models for demyelination with iPSC-derived OPCs demonstrated their survival and remyelinating capacity, but also revealed their limited migration capacity. In the present study, we induced overexpression of the polysialylating enzyme sialyltransferase X (STX) in iPSC-derived OPCs to stimulate the production of polysialic acid-neuronal cell adhesion molecules (PSA-NCAMs), known to promote and facilitate the migration of OPCs. The STX-overexpressing iPSC-derived OPCs showed a normal differentiation and maturation pattern and were able to downregulate PSA-NCAMs when they became myelin-forming oligodendrocytes. After implantation in the demyelinated corpus callosum of cuprizone-fed mice, STX-expressing iPSC-derived OPCs demonstrated a significant increase in migration along the axons. Our findings suggest that the reach and efficacy of iPSC-derived OPC transplantation can be improved by stimulating the OPC migration potential via specific gene modulation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
/
Oligodendroglia
/
Moléculas de Adesão de Célula Nervosa
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Células-Tronco Pluripotentes Induzidas
/
Células-Tronco Neurais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Stem Cells Transl Med
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Holanda