DNA Aptamer-Guided Glycomimetics for Developmental Stage-Specific Glycocalyx Engineering to Control Stem Cell...

Heparan sulfate glycosaminoglycans in the stem cell glycocalyx are crucial in controlling growth factor activity during development. Augmenting the surface of stem cells with synthetic heparan sulfate mimetics with defined compositions and growth factor binding profiles has emerged as a promising strategy to fine-tune cellular signaling responses and differentiation. However, current glycocalyx engineering methods lack specificity for stem cells or require prior genetic manipulation, limiting their applicability in a therapeutic context. Here, we report a heparan sulfate mimetic containing a DNA aptamer with affinity for the membrane-associated pluripotency marker, alkaline phosphatase, that can be selectively targeted to the surface of embryonic stem cells. The glycomimetic-enhanced fibroblast growth factor 2 recruitment to the stem cell surface activated signaling through the mitogen-activated protein kinase pathway and promoted neural differentiation. While the present work targets pluripotent cells specifically, it can be more broadly applicable to progenitor cells at other developmental stages to better control their differentiation and enhance their therapeutic potential.