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Advances in combined application of dental stem cells and small-molecule drugs in regenerative medicine

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Abstract

Teeth are a kind of masticatory organs of special histological origin, unique to vertebrates, playing an important role in chewing, esthetics, and auxiliary pronunciation. In the past decades, with the development of tissue engineering and regenerative medicine, the studies of mesenchymal stem cells (MSCs) gradually attracted the interest of researchers. Accordingly, several types of MSCs have been successively isolated in teeth or teeth-related tissues, including dental pulp stem cells, periodontal ligament stem cells, stem cells from human exfoliated deciduous teeth, dental follicle stem cells, stem cells from apical papilla and gingival mesenchymal stem cells. These dental stem cells (DSCs) are easily accessible, possess excellent stem cell characteristics, such as high proliferation rates and profound immunomodulatory properties. Small-molecule drugs are widely used and show great advantages in clinical practice. As research progressed, small-molecule drugs are found to have various complex effects on the characteristics of DSCs, especially the enhancement of biological characteristics of DSCs, which has gradually become a hot issue in the field of DSCs research. This review summarizes the background, current status, existing problems, future research directions, and prospects of the combination of DSCs with three common small-molecule drugs: aspirin, metformin, and berberine.

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Abbreviations

ALP:

Alkaline phosphatase

AMPK:

Adenosine monophosphate-activated protein kinase

BBR:

Berberine

BMMSCs:

Bone marrow mesenchymal stem cells

BMP10:

Bone morphogenetic protein 10

CM:

Conditioned medium

COL-1:

Collagen I

DFSCs:

Dental follicle stem cells

DMP1:

Dentin matrix acidic phosphoprotein 1

DPSCs:

Dental pulp stem cells

DSCs:

Dental stem cells

DSPP:

Dentin sialophosphoprotein

FGF9:

Fibroblast growth factor 9

GMSCs:

Gingival mesenchymal stem cells

IL-10:

Anti-inflammatory cytokine interleukin 10

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MSCs:

Mesenchymal stem cells

OCN:

Osteocalcin

OPN:

Osteopontin

PDLSCs:

Periodontal ligament stem cells

PEG-ASA:

Tetra-PEG hydrogels loaded with aspirin

PI3K/Akt:

Phosphoinositide 3-kinase-protein kinase B

PRF:

Platelet-rich fibrin

RUNX2:

Runt-related transcription factor 2

SCAPs:

Stem cells from apical papilla

SHED:

Stem cells from human exfoliated deciduous teeth

TCM:

Traditional Chinese medicine

TERT/Wnt/β-catenin:

Telomerase reverse transcriptase/wingless/integrated/β-catenin

TNF-α:

Tumor necrosis factor α

VEGFA:

Vascular endothelial growth factor A

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Funding

This work was supported by grants from the Natural Science Foundation of Shandong Province (No. ZR2021MH051 to Gang Ding), the National Natural Science Foundation of China (No. 81570945 to Gang Ding), the Postgraduate Education Quality Improvement Plan of Shandong Province (No. SDYAL21150 to Gang Ding), and 2021 Youth Innovation Talent Introduction and Education Program of Shandong Province Universities (The innovative team for molecular epidemiology of oral cancer based on multiomics).

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  1. School of Stomatology, Weifang Medical University, Baotong West Street No. 7166, Weifang, Shandong Province, China

    Zejun Zheng, Shuai Tang, Tong Yang, Xiaolan Wang & Gang Ding

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  1. Zejun Zheng
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  2. Shuai Tang
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  3. Tong Yang
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  4. Xiaolan Wang
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ZZ designed the study, searched literature, analyzed data, and wrote the article. ST, TY, and XW searched literature and analyzed data. GD designed the study, wrote the article, and supervised the study. All authors read and approved the final manuscript.

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Correspondence to Gang Ding.

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Zheng, Z., Tang, S., Yang, T. et al. Advances in combined application of dental stem cells and small-molecule drugs in regenerative medicine. Human Cell 36, 1620–1637 (2023). https://doi.org/10.1007/s13577-023-00943-1

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