RESUMEN
Replacing expensive and thermally unstable growth factors with synthetic alternatives has been an important issue in stem cell-based regenerative medicines. Here we developed DNA aptamer-assemblies that act as functional mimics of basic fibroblast growth factor (bFGF), one of the essential factors for stem cell culture. The most potent aptamer assembly named TD0, composed solely of 76-mer single-stranded DNA, could support the self-renewal and pluripotency of induced pluripotent stem cells (iPSCs). This work presents the first application of DNA aptamer in the maintenance of iPSCs.
Asunto(s)
Aptámeros de Nucleótidos/química , Materiales Biocompatibles/química , Aptámeros de Nucleótidos/metabolismo , Aptámeros de Nucleótidos/farmacología , Materiales Biocompatibles/metabolismo , Materiales Biocompatibles/farmacología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Factores de Crecimiento de Fibroblastos/química , Factores de Crecimiento de Fibroblastos/farmacología , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Fosforilación , Unión Proteica , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/agonistas , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
The reprogramming of receptor-ligand interactions affords an opportunity to direct cells to respond to user-defined external cues. Although this has often been achieved via the genetic engineering of receptors, an alternative, nongenetic approach is highly demanded. In this article, we propose the design of oligonucleotide-based synthetic switches that feature the ability to reprogram the ligand specificity of the growth factor receptor. We demonstrated that our synthetic switches induced growth factor signaling via the formation of the dynamic complex with specific external cues that would otherwise not induce the signaling. This chemical approach may be applied to designing a new class of chemical tools that can control the activities of native cells and represent smart and safer regenerative drugs.