Human Umbilical Cord Mesenchymal Stem Cell Differentiation Into Odontoblast-Like Cells and Endothelial Cells: A Potential Cell Source for Dental Pulp Tissue Engineering

Abstract

Objectives: Dental pulp regeneration is considered an ideal approach for treating dental pulp disease. Because pulp is composed of various cells, determining the proper seed cells is critical. We explored the potential of human umbilical cord mesenchymal stem cells (hUCMSCs) as seed cells for dental pulp regeneration. Methods: Liquid extract of human treated dentin matrix (LE-TDM) was acquired to culture hUCMSCs. Odontoblast-specific markers were detected by western blot, qRT-PCR, and immunofluorescence assays. Endothelial differentiation of hUCMSCs was examined according to VEGF induction by western blot, qRT-PCR, and Matrigel assays. hUCMSCs and VEGF-induced hUCMSCs (V-hUCMSCs) were also cocultured in vivo for the Matrigel plug assay and in vitro for RNA-sequencing (RNA-seq). Finally, encapsulated mono-cultured hUCMSCs or cocultured hUCMSCs and V-hUCMSCs in scaffolds were injected into the root segments and transplanted into immunodeficient mice for dental pulp regeneration. Results: Under LE-TDM induction, hUCMSCs expressed specific odontoblast markers (DSPP, DMP-1, DSP). Under VEGF induction, hUCMSCs expressed functional endothelial markers (CD31, eNOs, vWF). In vivo, the Matrigel plug assay indicated that cocultured hUCMSCs and V-hUCMSCs formed extensive vessel-like structures. RNA-seq results indicated that cocultured V-hUCMSCs exhibited high Hif-1 signaling pathway activity. Both the hUCMSCs mono-culture and coculture groups showed pulplike tissue regeneration. The cocultured group showed more extracellular matrix and vascularization than the mono-cultured group in vivo.

Hyaluronic Acid Facilitates Angiogenesis of Endothelial Colony Forming Cell Combining With Mesenchymal Stem Cell via CD44/ MicroRNA-139-5p Pathway

“…We considered that HA improved ECFCs viability through miR-139-5p in the HA-MSC-ECFC co-culture system. Generally, MSC could directional differentiated into endothelial cells in the medium supplemented with cytokines ( Wang et al, 2018 ; Zhang et al, 2020 ) and miRs participate in the process ( Arderiu et al, 2019 ). Decreased miR-139-5p expression in CD31 positive cells induced by HA may regulate target genes expression such as increased expression of VEGF and PDGF, which may further induced endothelial differentiation and proliferation.…”

Mesenchymal Stem Cells as a Cornerstone in a Galaxy of Intercellular Signals: Basis for a New Era of Medicine

“…Therefore, stem cell-based therapies would be an improving approach to repair or replace the damaged or lost tissues of teeth in order to recover the morphological and biological functions [ 204 ]. Recently, it was shown that UC-MSC possess the ability to differentiate into odontoblast-like cells under the microenvironment induced by a liquid extract of human treated dentin matrix in vitro [ 205 ]. On the other hand, we consider the possibility that MSC secretome-derived products, such as conditioned medium and/or exosomes, may be a new strategy to induce dental stem cells to dent pulp regeneration, which will require further well-designed investigation.…”

Human umbilical cord mesenchymal stem cell promotes angiogenesis via integrin β1/ERK1/2/HIF-1α/VEGF-A signaling pathway for off-the-shelf breast tissue engineering

“…The differentiation and proliferation of stem cells is influenced by the microenvironment, also called the “stem cell niche” [ 21 ]. Most recently, a study revealed that hUCMSCs could differentiate into odontoblast-like cell via human dentin matrix [ 22 ]. The inserted adipose tissue also underwent neoadipogenesis, which was potentially driven by the stem cell and native adipose extracellular matrix.…”