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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization
Fei Liu, Jing Xiao, Lei-Hui Chen, Yu-Yue Pan, Jun-Zhang Tian, Zhi-Ren Zhang, Xiao-Chun Bai
Fei Liu, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Fei Liu, Jun-Zhang Tian, Department of Health Management, Guangdong Second Provincial General Hospital, Guangzhou 510317, Guangdong Province, China
Jing Xiao, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People’s Hospital Affiliated with Jinan University, Zhuhai 519000, Guangdong Province, China
Jing Xiao, Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau 999078, China
Lei-Hui Chen, Yu-Yue Pan, Department of Stomatology, Guangdong Second Provincial General Hospital, Guangzhou 510317, Guangdong Province, China
Zhi-Ren Zhang, Zhuhai Institute of Translational Medicine, Zhuhai Hospital Affiliated with Jinan University, Zhuhai 519000, Guangdong Province, China
Xiao-Chun Bai, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Co-first authors: Fei Liu and Jing Xiao.
Co-corresponding authors: Zhi-Ren Zhang and Chun-Xiao Bai.
Author contributions: Liu F, Xiao J, Tian JZ, Zhang ZR, and Bai XC designed the research; Liu F and Xiao J performed the research and analyzed the data; Chen LH and Pan YY contributed human dental pulp tissue; Liu F wrote the paper. Liu F and Xiao J contributed to the work equally and should be regarded as co-first authors. Bai XC and Zhang ZR contributed to the work equally and should be regarded as co-corresponding author.
Supported by the Science and Technology Programme of Guangzhou City, No. 202201020341.
Institutional review board statement: This study was approved by the Ethics Committee of Guangdong Second Provincial General Hospital.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at kqliufei@126.com. Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Xiao-Chun Bai, PhD, Professor, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, No. 1023-1063 Shatai South Road, Baiyun District, Guangzhou 510515, Guangdong Province, China. baixc15@smu.edu.cn
Received: December 19, 2023
Peer-review started: December 19, 2023
First decision: January 12, 2024
Revised: January 21, 2024
Accepted: February 28, 2024
Article in press: February 28, 2024
Published online: March 26, 2024
Processing time: 96 Days and 18.9 Hours
ARTICLE HIGHLIGHTS
Research background
Stem cells can self-organise into microsized organ units, which can partially model tissue function and regeneration. Dental pulp organoids have been used to replicate the processes of tooth development and related diseases. However, the lack of vasculature limits the usefulness of dental pulp organo.
Research motivation
The survival of stem cell transplants should be promoted, thereby improving the repair ability of the cells.
Research objectives
Three-dimensional (3D) self-assembly of a novel vascularised dental pulp-like organoid in vitro by hypoxia and conditioned media.
Research methods
Human dental pulp stem cells were induced from endothelial cells (ECs) through exposure to a hypoxic environment and conditioned medium. The resulting cells were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce Vorganoids. The biological characteristics of the Vorganoids were analysed, and the regulatory pathways associated with angiogenesis were studied.
Research results
Vorganoids are similar in morphology and function to dental pulp tissue. Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were performed to identify the involvement of the biomarkers forkhead box protein O1 (FOXO1) and fibroblast growth factor 2 (FGF2) in key regulatory pathways associated with Vorganoid angiogenesis.
Research conclusions
In this study, we effectively established an in vitro model of prevascularized dental pulp organoids and used it to elucidate novel mechanisms of angiogenesis during dental regeneration. The biomarkers FOXO1 and FGF2 confirmed the angiogenesis-regulating role of angiopoietins.
Research perspectives
This innovative study has effectively established an in vitro model of prevascularized dental pulp organoids and used it to elucidate new mechanisms of angiogenesis during regeneration, facilitating the development of clinical treatment strategies.
