Glycoengineering human neural stem cells (hNSCs) for adhesion improvement using a novel thiol-modified N-acetylmannosamine (ManNAc) analog

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

This study sets the stage for the therapeutic use of Ac 5 ManNTProp, an N-acetylmannosamine (ManNAc) analog that installs thiol-modified sialoglycans onto the surfaces of human neural stem cells (hNSC). First, we compared hNSC adhesion to the extracellular matrix (ECM) proteins laminin, fibronectin, and collagen and found preferential adhesion and concomitant changes to cell morphology and cell spreading for Ac 5 ManNTProp-treated cells to laminin, compared to fibronectin where there was a modest response, and collagen where there was no observable increase. PCR array transcript analysis identified several classes of cell adhesion molecules that responded to combined Ac 5 ManNTProp treatment and hNSC adhesion to laminin. Of these, we focused on integrin α6β1 expression, which was most strongly upregulated in analog-treated cells incubated on laminin. We also characterized downstream responses including vinculin display as well as the phosphorylation of focal adhesion kinase (FAK) and extracellular signal-related kinase (ERK). In these experiments, Ac 5 ManNTProp more strongly induced all tested biological endpoints compared to Ac 5 ManNTGc, showing that the single methylene unit that structurally separates the two analogs finely tunes biological responses. Together, the concerted modulation of multiple pro-regenerative activities through Ac 5 ManNTProp treatment, in concert wit

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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