PDGF-BB overexpressing dental pulp stem cells improve angiogenesis in dental pulp regeneration

Wentao Jiang; Wentao Jiang; Wentao Jiang; Wentao Jiang; Shuhan Duan; Shuhan Duan; Shuhan Duan; Shuhan Duan; Weiping Li; Huijiao Yan; Huijiao Yan; Huijiao Yan; Huijiao Yan; Chenli Si; Chenli Si; Chenli Si; Ningwei Xu; Ningwei Xu; Ningwei Xu; Ningwei Xu; Yishuai Li; Yishuai Li; Yishuai Li; Yishuai Li; Wenjie Zhang; Wenjie Zhang; Wenjie Zhang; Wenjie Zhang; Shensheng Gu; Shensheng Gu; Shensheng Gu; Shensheng Gu

doi:10.3389/fbioe.2025.1578410

Frontiers in Bioengineering and Biotechnology (Apr 2025)

PDGF-BB overexpressing dental pulp stem cells improve angiogenesis in dental pulp regeneration

Wentao Jiang,
Wentao Jiang,
Wentao Jiang,
Wentao Jiang,
Shuhan Duan,
Shuhan Duan,
Shuhan Duan,
Shuhan Duan,
Weiping Li,
Huijiao Yan,
Huijiao Yan,
Huijiao Yan,
Huijiao Yan,
Chenli Si,
Chenli Si,
Chenli Si,
Ningwei Xu,
Ningwei Xu,
Ningwei Xu,
Ningwei Xu,
Yishuai Li,
Yishuai Li,
Yishuai Li,
Yishuai Li,
Wenjie Zhang,
Wenjie Zhang,
Wenjie Zhang,
Wenjie Zhang,
Shensheng Gu,
Shensheng Gu,
Shensheng Gu,
Shensheng Gu

Affiliations

Wentao Jiang: Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Wentao Jiang: College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
Wentao Jiang: National Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, China
Wentao Jiang: Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
Shuhan Duan: Department of Oral Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shuhan Duan: College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
Shuhan Duan: National Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, China
Shuhan Duan: Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
Weiping Li: The Affiliated Stomatological Hospital of Nanjing Medical University, State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China
Huijiao Yan: Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Huijiao Yan: College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
Huijiao Yan: National Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, China
Huijiao Yan: Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
Chenli Si: Department of Dermatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Chenli Si: National Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, China
Chenli Si: Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
Ningwei Xu: Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Ningwei Xu: College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
Ningwei Xu: National Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, China
Ningwei Xu: Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
Yishuai Li: Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yishuai Li: College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
Yishuai Li: National Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, China
Yishuai Li: Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
Wenjie Zhang: Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Wenjie Zhang: College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
Wenjie Zhang: National Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, China
Wenjie Zhang: Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
Shensheng Gu: Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shensheng Gu: College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
Shensheng Gu: National Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, China
Shensheng Gu: Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China

DOI: https://doi.org/10.3389/fbioe.2025.1578410
Journal volume & issue: Vol. 13

Abstract

Read online

IntroductionAngiogenesis represents a critical challenge in dental pulp regeneration due to the tissue’s restricted nutrient supply through a 0.5-mm apical foramen. While dental pulp stem cells (DPSCs) hold regenerative potential, their limited vascularization capacity impedes clinical applications. Through Single-cell RNA sequencing (scRNA-seq) analysis of human dental pulp, we discovered a PDGF (+) mesenchymal subset exhibiting enhanced angiogenic signatures, suggesting targeted cell selection could overcome this bottleneck.MethodsScRNA-seq identified PDGF (+) subpopulation in human pulp samples, validated through multiplex immunohistochemical of the localization of PDGF/CD73/CD31. PDGF-BB-overexpressing DPSCs were engineered via lentiviral vectors. Functional assessments included: 1) CCK-8/Edu/cell cycle/transwell assays for proliferation and migration ability 2) HUVECs co-culture models analyzing chemotaxis and tube formation 3) Vascularized tissue formation in rat kidney capsule transplants.Results and DiscussionThe CD73 (+) PDGF (+) subpopulation demonstrated spatial correlation with CD31 (+) vasculature. PDGF-BB overexpression enhanced DPSCs' proliferative capacity and migration capacity. Co-cultured HUVECs exhibited increased tube formation with PDGF-BB group. In vivo transplants generated more vascular structures containing CD31 (+) endothelia. These findings establish PDGF-BB engineering as an effective strategy to amplify DPSCs' angiogenic potential, while emphasizing the therapeutic value of functionally-defined stem cell subpopulations in pulp regeneration.

Published in Frontiers in Bioengineering and Biotechnology

ISSN: 2296-4185 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Technology: Chemical technology: Biotechnology
Website: http://www.frontiersin.org/bioengineering_and_biotechnology

About the journal

Abstract

Keywords