ArticleStem cell research & therapy2025
Semaphorin-4D signaling in recruiting dental stem cells for vascular stabilization.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- The Interplay of M1 Macrophages and Dental Pulp Stem Cells Promotes Angiogenesis Through IL-8-Dependent VEGF Regulation: An In Vitro Study.International endodontic journal · 2026Article
- Context-Dependent Roles of the Plexin-B Family Across Neurological, Oncological, Immune and Cardiovascular Disorders: Mechanisms and Therapeutic Implications.Life (Basel, Switzerland) · 2026Review
- METTL3 mediates mJournal of advanced research · 2026Article
- Stimuli-responsive hydrogels based on cascade reactions: a novel strategy to promote the efficient repair of diabetic wounds.Theranostics · 2026Review
- Angiogenic regulation of dental pulp stem cells.Frontiers in dental medicine · 2025Review
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Authors and funding
6 authors.
Funding
Abstract
backgroundAchieving a stable vasculature is crucial for tissue regeneration. Endothelial cells initiate vascular morphogenesis, followed by mural cells that stabilize new vessels. This study investigated the in vivo effects of Sema4D-Plexin-B1 signaling on stem cells from human exfoliated deciduous teeth (SHED)-supported angiogenesis, focusing on its mechanism in PDGF-BB secretion. We also explored macrophages as an endogenous source of Sema4D for vascular stabilization.
methodsThe in vivo Matrigel plug angiogenesis assay was conducted to examine the impact of Sema4D on vessel formation and stabilization supported by SHED. Knockdown of Plexin-B1 in human umbilical vein endothelial cells (HUVECs) and PDGFR-β inhibitors were utilized to explore the fundamental regulatory mechanisms. Furthermore, the m6A methylation levels of total RNA and the expression of Methyltransferase-like 3 (METTL3) were assessed under conditions of Sema4D treatment in vitro. An ELISA was employed to measure the levels of Sema4D in the supernatants derived from THP-1 cell-mediated macrophages. Additionally, a three-dimensional vasculature-on-a-chip microfluidic device was used to investigate the role of M2c macrophage-derived Sema4D in the stabilization of vascular structures.
resultsSema4D induced the formation of a greater number of perfused vessels by HUVECs and enhanced the coverage of these vessels by SM22α-positive SHED (SM22α
conclusionsSema4D acts on Plexin-B1, inducing METTL3-mediated PDGF-BB secretion to recruit SHED to stabilize vessels. Macrophages could be a key source of Sema4D for vascular stabilization.
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Registered trials
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