ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Stem Cell Research
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1630129
This article is part of the Research TopicAdvances in Dental Pulp Stem Cell Biology and ApplicationsView all 6 articles
DMP1-mediated transformation of DPSCs to CD31⁺/CD144⁺ cells demonstrate endothelial Phenotype both in vitro and in vivo
Provisionally accepted
- University of Illinois Chicago, Chicago, United States
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Dental pulp stem cells (DPSCs), have the potential ability to differentiate into endothelial cells (ECs), offering a promising way to create new blood vessels, which is crucial for improving tissue repair and regeneration. Many studies have focused on optimizing endothelial cell differentiation of DPSCs in vitro and subsequent validation of the vasculogenic potential of newly generated ECs in vivo. Previously, we demonstrated that combining stimulation of Dentin Matrix Protein-1 (DMP1) with biological cues from the extracellular matrix (ECM) of human umbilical vein endothelial cells (HUVEC) greatly enhances the transformation of DPSCs into ECs. As DPSCs are a promising source for potential therapeutic applications, in various tissue regeneration applications, this study involved sorting DMP1-treated DPSCs using angiogenic specific markers CD31 and CD144. The cells were separated into a positive fraction (CD31⁺/CD144⁺) and a negative fraction (CD31⁻/CD144⁻). To assess if ECs transformed from DMP1 stimulated DPSCs maintain their endothelial properties over time, we cultured both the positive CD31⁺/CD144⁺ and negative CD31⁻/CD144⁻ fractions along with unstimulated DPSCs and assessed their angiogenic characteristics by gene expression analysis, functional properties using a tubule formation assay. The findings of this study indicate that the CD31⁺/CD144⁺ fraction, derived from DMP1-induced ECs from DPSCs, retains both the phenotypic and functional characteristics of ECs, in contrast to the CD31⁻/CD144⁻ fraction. Furthermore, in vivo analysis of the sorted ECs using the subcutaneous implantation model explains their typical vascular function through neovascularization and the expression of vasculogenic markers. Overall, DPSC-derived ECs obtained by stimulation with DMP1 function as typical vascular ECs demonstrating the development of therapeutic potential for tissue repair and regeneration.
Keywords: dental pulp stem cells, Dentin matrix protein 1, Human vascular endothelial cells, Endothelial Cells, Endothelial cell phenotype, Angiogenesis
Received: 16 May 2025; Accepted: 17 Jul 2025.
Copyright: © 2025 Ganapathy, Chen, Bakthavachalam and GEORGE. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: ANNE GEORGE, University of Illinois Chicago, Chicago, United States
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