Cystamine-terminated poly(beta-amino ester)s for siRNA delivery to human mesenchymal stem cells and enhancement of osteogenic differentiation.
Biomaterials
; 33(32): 8142-51, 2012 Nov.
Article
en En
| MEDLINE
| ID: mdl-22871421
ABSTRACT
Enhancing human mesenchymal stem cell (hMSC) differentiation via RNA interference (RNAi) could provide an effective way of controlling cell fate for tissue engineering, but a safe and effective delivery vehicle must first be developed. Here, we evaluated an array of synthetic end-modified poly(beta-amino ester) (PBAE)-based nanoparticles to optimize siRNA delivery into hMSCs. In general, cystamine-terminated polymers caused the most knockdown, with the best polymer achieving 91% knockdown 20 days post-transfection. Binding studies revealed that the cystamine-terminated polymer bound siRNA tightly at lower weight ratios of polymer to siRNA but then efficiently released siRNA upon exposure to a reducing environment, suggesting that this class of PBAEs can form tight initial interactions with its cargo and then cause efficient, environmentally-triggered release in the cytoplasm. Finally, we tested a functional application of this system by transfecting hMSCs with siRNA against an inhibitor of osteogenesis, B-cell lymphoma (Bcl)-like protein 2 (BCL2L2). This resulted in enhanced osteogenesis over 4 weeks as evidenced by Alizarin Red S staining and calcium quantification. The bioreducible PBAE/siRNA nanoparticles developed here can provide a means of safe and effective control of hMSC differentiation for a wide variety of applications.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteogénesis
/
Polímeros
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Transfección
/
Cistamina
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ARN Interferente Pequeño
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Células Madre Mesenquimatosas
Límite:
Humans
Idioma:
En
Revista:
Biomaterials
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos