Enhancing Vasculogenesis in Dental Pulp Development: DPSCs-ECs Communication Via FN1-ITGA5 Signaling

Overview

Journal Stem Cell Rev Rep

Publisher Springer

Specialty Cell Biology

Date 2024 Feb 28

PMID 38418738

Authors

Tiankai Di

Chao Feng

Lulu Wang

Jinlong Xu

Yang Du

Baixiang Cheng

Yujiang Chen

Lian Wu

Affiliations

Soon will be listed here.

Abstract

Background: Dental pulp regeneration therapy is a challenge to achieve early vascularization during treatment. Studying the regulatory mechanisms of vascular formation during human dental pulp development may provide insights for related therapies. In this study, we utilized single-cell sequencing analysis to compare the gene expression of dental pulp stem cells (DPSCs) and vascular endothelial cells (ECs) from developing and mature dental pulps.

Method: Immunohistochemistry, Western blot, and real-time polymerase chain reaction (RT-PCR) were used to detect fibronectin 1 (FN1) expression and molecules, such as PI3K/AKT. Cell proliferation assay, scratch assay, tube formation assay and were used to investigate the effects of DPSCs on the vasculogenetic capability of ECs. Additionally, animal experiments involving mice were conducted.

Result: The results revealed that DPSCs exist around dental pulp vasculature. FN1 expression was significantly higher in DPSCs from young permanent pulps than mature pulps, promoting HUVEC proliferation, migration, and tube formation via ITGA5 and the downstream PI3K/AKT signaling pathway.

Conclusion: Our data indicate that intercellular communication between DPSCs and ECs mediated by FN1-ITGA5 signaling is crucial for vascularizationduring dental pulp development, laying an experimental foundation for future clinical studies.

References

Tonnesen M, Feng X, Clark R . Angiogenesis in wound healing. J Investig Dermatol Symp Proc. 2001; 5(1):40-6. DOI: 10.1046/j.1087-0024.2000.00014.x. View

Shi C, Li Z, Wu Y, Li X, Li Y, Wei J . Euscaphic acid and Tormentic acid protect vascular endothelial cells against hypoxia-induced apoptosis via PI3K/AKT or ERK 1/2 signaling pathway. Life Sci. 2020; 252:117666. DOI: 10.1016/j.lfs.2020.117666. View

Gronthos S, Mankani M, Brahim J, Robey P, Shi S . Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A. 2000; 97(25):13625-30. PMC: 17626. DOI: 10.1073/pnas.240309797. View

Bedzhov I, Zernicka-Goetz M . Self-organizing properties of mouse pluripotent cells initiate morphogenesis upon implantation. Cell. 2014; 156(5):1032-44. PMC: 3991392. DOI: 10.1016/j.cell.2014.01.023. View

Zou T, Jiang S, Zhang Y, Liu J, Yi B, Qi Y . In Situ Oxygen Generation Enhances the SCAP Survival in Hydrogel Constructs. J Dent Res. 2021; 100(10):1127-1135. DOI: 10.1177/00220345211027155. View

Chrepa V, Austah O, Diogenes A . Evaluation of a Commercially Available Hyaluronic Acid Hydrogel (Restylane) as Injectable Scaffold for Dental Pulp Regeneration: An In Vitro Evaluation. J Endod. 2017; 43(2):257-262. DOI: 10.1016/j.joen.2016.10.026. View

Xuan K, Li B, Guo H, Sun W, Kou X, He X . Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth. Sci Transl Med. 2018; 10(455). DOI: 10.1126/scitranslmed.aaf3227. View

Schmalz G, Widbiller M, Galler K . Clinical Perspectives of Pulp Regeneration. J Endod. 2020; 46(9S):S161-S174. DOI: 10.1016/j.joen.2020.06.037. View

Liu W, Yuan Y, Liu D . Extracellular Vesicles from Adipose-Derived Stem Cells Promote Diabetic Wound Healing via the PI3K-AKT-mTOR-HIF-1α Signaling Pathway. Tissue Eng Regen Med. 2021; 18(6):1035-1044. PMC: 8599548. DOI: 10.1007/s13770-021-00383-8. View

10.

Ma D, Gao J, Yue J, Yan W, Fang F, Wu B . Changes in proliferation and osteogenic differentiation of stem cells from deep caries in vitro. J Endod. 2012; 38(6):796-802. DOI: 10.1016/j.joen.2012.02.014. View

11.

Krivanek J, Soldatov R, Kastriti M, Chontorotzea T, Herdina A, Petersen J . Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth. Nat Commun. 2020; 11(1):4816. PMC: 7511944. DOI: 10.1038/s41467-020-18512-7. View

12.

Li Z, Wu M, Liu S, Liu X, Huan Y, Ye Q . Apoptotic vesicles activate autophagy in recipient cells to induce angiogenesis and dental pulp regeneration. Mol Ther. 2022; 30(10):3193-3208. PMC: 9552912. DOI: 10.1016/j.ymthe.2022.05.006. View

13.

Zhang Y, Liu J, Zou T, Qi Y, Yi B, Dissanayaka W . DPSCs treated by TGF-β1 regulate angiogenic sprouting of three-dimensionally co-cultured HUVECs and DPSCs through VEGF-Ang-Tie2 signaling. Stem Cell Res Ther. 2021; 12(1):281. PMC: 8112067. DOI: 10.1186/s13287-021-02349-y. View

14.

Chen Y, Ma Y, Yang X, Chen J, Yang B, Tian W . The Application of Pulp Tissue Derived-Exosomes in Pulp Regeneration: A Novel Cell-Homing Approach. Int J Nanomedicine. 2022; 17:465-476. PMC: 8809678. DOI: 10.2147/IJN.S342685. View

15.

Ku C, Ho T, Huang C, Chu P, Ou H, Hsieh P . Cordycepin Attenuates Palmitic Acid-Induced Inflammation and Apoptosis of Vascular Endothelial Cells through Mediating PI3K/Akt/eNOS Signaling Pathway. Am J Chin Med. 2021; 49(7):1703-1722. DOI: 10.1142/S0192415X21500804. View

16.

Ruan Q, Tan S, Guo L, Ma D, Wen J . Prevascularization techniques for dental pulp regeneration: potential cell sources, intercellular communication and construction strategies. Front Bioeng Biotechnol. 2023; 11:1186030. PMC: 10232868. DOI: 10.3389/fbioe.2023.1186030. View

17.

Li C, Qin T, Jin Y, Hu J, Yuan F, Cao Y . Cerebrospinal fluid-derived extracellular vesicles after spinal cord injury promote vascular regeneration via PI3K/AKT signaling pathway. J Orthop Translat. 2023; 39:124-134. PMC: 9999163. DOI: 10.1016/j.jot.2023.02.001. View

18.

Zhang X, Chen F, Huang P, Wang X, Zhou K, Zhou C . Exosome-depleted MiR-148a-3p derived from Hepatic Stellate Cells Promotes Tumor Progression via ITGA5/PI3K/Akt Axis in Hepatocellular Carcinoma. Int J Biol Sci. 2022; 18(6):2249-2260. PMC: 8990464. DOI: 10.7150/ijbs.66184. View

19.

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

20.

Gurtner G, Werner S, Barrandon Y, Longaker M . Wound repair and regeneration. Nature. 2008; 453(7193):314-21. DOI: 10.1038/nature07039. View