International journal of oral scienceJul 23, 2026

Improving tooth pulp healing by changing metabolism in mature dental stem cells using GLUT1 and HK2 mRNA

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Updated Jul 24, 2026

Abstract

Reprogrammed mature dental pulp stem cells (DPSCs) achieved a vessel density of 10.2 vessels per mm², 2.5-fold higher than untreated controls.

Aged DPSCs show reduced ability to support blood vessel formation due to impaired energy production.
Decreased expression of glucose transporter type 1 (GLUT1) and hexokinase 2 (HK2) contributes to this impairment.
Using a specialized delivery system, over 90% of GLUT1 and HK2 mRNA were effectively introduced into mature DPSCs.
Conditioned medium from reprogrammed DPSCs increased capillary length by 2.0 times and branch points by 2.3 times, indicating restored blood vessel formation capability.
In a tooth root slice model, reprogrammed DPSCs generated tissue with vascularization levels similar to those of immature DPSCs.

Simplified

The age-related decline in the pro-angiogenic capacity of mature dental pulp stem cells (DPSCs) severely limits pulp regeneration. We identify impaired glycolytic metabolism, driven by reduced glucose transporter type 1 (GLUT1) and hexokinase 2 (HK2) expression, as the key mechanism, as its inhibition diminished endothelial tube formation. To reverse this, we developed an aminolyzed highly branched poly(β-amino ester) (HBPA) as a vector for GLUT1/HK2 mRNA co-delivery, achieving >90% transfection efficiency with excellent biocompatibility. In vitro, conditioned medium from reprogrammed mature DPSCs resulted in a 2.0-fold increase in capillary length and a 2.3-fold increase in branch points, restoring angiogenic potential to levels equivalent to those of immature DPSCs. This efficacy translated robustly in vivo, where a tooth root slice model showed reprogrammed cells generated tissue with a vessel density of 10.2 vessels per mm², 2.5-fold higher than that of untreated controls. Crucially, this level of vascularization was statistically indistinguishable from that achieved by the benchmark immature DPSCs. Our study demonstrates that HBPA-mediated metabolic reprogramming effectively rejuvenates mature DPSCs by restoring the "Metabolic-ECM-Angiogenesis Axis", offering a translatable strategy for predictable, vascularized pulp regeneration.

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PubMed

Improving tooth pulp healing by changing metabolism in mature dental stem cells using GLUT1 and HK2 mRNA

Abstract

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