PDGF-BB overexpressing dental pulp stem cells improve angiogenesis in dental pulp regeneration
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....
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-04-01
|
| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1578410/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849712667014463488 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Wentao Jiang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cd571a62f4ab412aba80c0ab5f4e76f2 |
| institution | DOAJ |
| issn | 2296-4185 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj-art-cd571a62f4ab412aba80c0ab5f4e76f22025-08-20T03:14:12ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852025-04-011310.3389/fbioe.2025.15784101578410PDGF-BB overexpressing dental pulp stem cells improve angiogenesis in dental pulp regenerationWentao Jiang0Wentao Jiang1Wentao Jiang2Wentao Jiang3Shuhan Duan4Shuhan Duan5Shuhan Duan6Shuhan Duan7Weiping Li8Huijiao Yan9Huijiao Yan10Huijiao Yan11Huijiao Yan12Chenli Si13Chenli Si14Chenli Si15Ningwei Xu16Ningwei Xu17Ningwei Xu18Ningwei Xu19Yishuai Li20Yishuai Li21Yishuai Li22Yishuai Li23Wenjie Zhang24Wenjie Zhang25Wenjie Zhang26Wenjie Zhang27Shensheng Gu28Shensheng Gu29Shensheng Gu30Shensheng Gu31Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCollege of Stomatology, Shanghai Jiao Tong University, Shanghai, ChinaNational Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, ChinaShanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, ChinaDepartment of Oral Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCollege of Stomatology, Shanghai Jiao Tong University, Shanghai, ChinaNational Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, ChinaShanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, ChinaThe 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, ChinaDepartment of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCollege of Stomatology, Shanghai Jiao Tong University, Shanghai, ChinaNational Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, ChinaShanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, ChinaDepartment of Dermatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaNational Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, ChinaShanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, ChinaDepartment of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCollege of Stomatology, Shanghai Jiao Tong University, Shanghai, ChinaNational Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, ChinaShanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, ChinaDepartment of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCollege of Stomatology, Shanghai Jiao Tong University, Shanghai, ChinaNational Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, ChinaShanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, ChinaDepartment of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCollege of Stomatology, Shanghai Jiao Tong University, Shanghai, ChinaNational Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, ChinaShanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, ChinaDepartment of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCollege of Stomatology, Shanghai Jiao Tong University, Shanghai, ChinaNational Center for Stomatology and National Clinical Research Center for Oral Diseases, Shanghai, ChinaShanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, ChinaIntroductionAngiogenesis 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.https://www.frontiersin.org/articles/10.3389/fbioe.2025.1578410/fulldental pulp stem cellsvascularizationsingle-cell RNA sequencingendothelialdental pulp regeneration |
| spellingShingle | 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 PDGF-BB overexpressing dental pulp stem cells improve angiogenesis in dental pulp regeneration Frontiers in Bioengineering and Biotechnology dental pulp stem cells vascularization single-cell RNA sequencing endothelial dental pulp regeneration |
| title | PDGF-BB overexpressing dental pulp stem cells improve angiogenesis in dental pulp regeneration |
| title_full | PDGF-BB overexpressing dental pulp stem cells improve angiogenesis in dental pulp regeneration |
| title_fullStr | PDGF-BB overexpressing dental pulp stem cells improve angiogenesis in dental pulp regeneration |
| title_full_unstemmed | PDGF-BB overexpressing dental pulp stem cells improve angiogenesis in dental pulp regeneration |
| title_short | PDGF-BB overexpressing dental pulp stem cells improve angiogenesis in dental pulp regeneration |
| title_sort | pdgf bb overexpressing dental pulp stem cells improve angiogenesis in dental pulp regeneration |
| topic | dental pulp stem cells vascularization single-cell RNA sequencing endothelial dental pulp regeneration |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1578410/full |
| work_keys_str_mv | AT wentaojiang pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT wentaojiang pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT wentaojiang pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT wentaojiang pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT shuhanduan pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT shuhanduan pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT shuhanduan pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT shuhanduan pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT weipingli pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT huijiaoyan pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT huijiaoyan pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT huijiaoyan pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT huijiaoyan pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT chenlisi pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT chenlisi pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT chenlisi pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT ningweixu pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT ningweixu pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT ningweixu pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT ningweixu pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT yishuaili pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT yishuaili pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT yishuaili pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT yishuaili pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT wenjiezhang pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT wenjiezhang pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT wenjiezhang pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT wenjiezhang pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT shenshenggu pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT shenshenggu pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT shenshenggu pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration AT shenshenggu pdgfbboverexpressingdentalpulpstemcellsimproveangiogenesisindentalpulpregeneration |