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The proangiogenic effects of extracellular vesicles secreted by dental pulp stem cells derived from periodontally compromised teeth.
Zhou, Huan; Li, Xuan; Yin, Yuan; He, Xiao-Tao; An, Ying; Tian, Bei-Min; Hong, Yong-Long; Wu, Li-An; Chen, Fa-Ming.
Afiliação
  • Zhou H; State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
  • Li X; State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
  • Yin Y; State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
  • He XT; State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
  • An Y; State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
  • Tian BM; State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
  • Hong YL; Stomatology Center, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, People's Republic of China. ylhong93@163.com.
  • Wu LA; State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China. lianwu@fmmu.edu.cn.
  • Chen FM; State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China. cfmsunhh@fmmu.edu.cn.
Stem Cell Res Ther ; 11(1): 110, 2020 03 06.
Article em En | MEDLINE | ID: mdl-32143712
BACKGROUND: Although dental pulp stem cells (DPSCs) isolated from periodontally compromised teeth (P-DPSCs) have been demonstrated to retain pluripotency and regenerative potential, their use as therapeutics remains largely unexplored. In this study, we investigated the proangiogenic effects of extracellular vesicles (EVs) secreted by P-DPSCs using in vitro and in vivo testing models. METHODS: Patient-matched DPSCs derived from periodontally healthy teeth (H-DPSCs) were used as the control for P-DPSCs. Conditioned media (CMs) derived from H-DPSCs and P-DPSCs (H-CM and P-CM), CMs derived from both cell types pretreated with the EV secretion blocker GW4869 (H-GW and P-GW), and EVs secreted by H-DPSCs and P-DPSCs (H-EVs and P-EVs) were prepared to test their proangiogenic effects on endothelial cells (ECs). Cell proliferation, migration, and tube formation were assessed using the Cell Counting Kit-8 (CCK-8), transwell/scratch wound healing, and Matrigel assays, respectively. Specifically, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blot analysis were used to examine the expression levels of angiogenesis-related genes/proteins in ECs in response to EV-based incubation. Finally, a full-thickness skin defect model was applied to test the effects of EVs on wound healing and new vessel formation. RESULTS: Both H-CM and P-CM promoted EC angiogenesis, but the proangiogenic effects were compromised when ECs were incubated in H-GW and P-GW, wherein the EV secretion was blocked by pretreatment with GW4869. In EV-based incubations, although both H-EVs and P-EVs were found to enhance the angiogenesis-related activities of ECs, P-EVs exerted a more robust potential to stimulate EC proliferation, migration, and tube formation. In addition, P-EVs led to higher expression levels of angiogenesis-related genes/proteins in ECs than H-EVs. Similarly, both P-EVs and H-EVs were found to accelerate wound healing and promote vascularization across skin defects in mice, but wounds treated with P-EVs resulted in a quicker healing outcome and enhanced new vessel formation. CONCLUSIONS: The findings of the present study provide additional evidence that P-DPSCs derived from periodontally diseased teeth represent a potential source of cells for research and therapeutic use. Particularly, the proangiogenic effects of P-EVs suggest that P-DPSCs may be used to promote new vessel formation in cellular therapy and regenerative medicine.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Endoteliais / Vesículas Extracelulares Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Endoteliais / Vesículas Extracelulares Idioma: En Ano de publicação: 2020 Tipo de documento: Article