Work

Perivascular Niche and Self-renewal of Dental Pulp Stem Cells

Year: 2020

Type: article

Abstract: Interactions with the microenvironment modulate the fate of stem cells in perivascular niches in tissues (e.g. bone) and organs (e.g. liver). However, the functional relevance of the molecular crosstalk between endothelial cells and stem cells within the perivascular niche in dental pulps is unclear. Here, we tested the hypothesis that endothelial cell-initiated signaling is necessary to maintain self-renewal of dental pulp stem cells. First, we show preferential localization of cells that express high levels of self-renewal stem cell markers (i.e. ALDH1 and Bmi-1) in physiological human dental pulps. Then, through an in vitro functional assay for self-renewal (i.e. secondary orosphere assay), we show that endothelial cell-derived factors promote self-renewal of dental pulp stem cells. Mechanistic studies demonstrated that endothelial cell-derived Interleukin (IL)-6 induces expression of Bmi-1 in dental pulp stem cells through the STAT3 signaling pathway. STAT3-silenced dental pulp stem cells (stably transduced with shRNA-STAT3) seeded in biodegradable scaffolds and transplanted into immunodeficient mice generated fewer perivascular niches comprised of endothelial cells and stem cells exhibiting features of self-renewal. In vitro capillary sprouting assays revealed that inhibition of IL-6 or STAT3 signaling decreases the vasculogenic potential of dental pulp stem cells, suggesting its importance in the establishment of the perivascular niche. Collectively, these data demonstrate that endothelial cell-derived factors mediate self-renewal of dental pulp stem cells through STAT3 signaling and induction of Bmi-1. Overall, these data suggest that a crosstalk between endothelial cells and stem cells within the perivascular niche is required for the maintenance of stem cell pools in dental pulp.

Source: Deep Blue (University of Michigan)

Author: Min Oh

Language: English

Topic: Mesenchymal stem cell research

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, Medical School, University of Michigan, National Institute of Dental and Craniofacial Research

Awards: G1816531886, Perivascular Niche and Self-Renewal of Dental Pulp Stem Cells, Mechanisms of dental pulp stem cell differentiation into functional endothelium, Tissue Engineering and Regeneration

OpenAlex ID: W3096925641

FWCI:

Cites: 77

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Related to: 10