Multicellular Spheroids Formation on Hydrogel Enhances Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells Under Magnetic Nanoparticles Induction

Xiao Han,1,2 Shijia Tang,1 Lin Wang,1 Xueqin Xu,2 Ruhan Yan,2 Sen Yan,3 Zhaobin Guo,4 Ke Hu,1,2 Tingting Yu,5 Mengping Li,2 Yuqin Li,2 Feimin Zhang,1,2 Ning Gu2,3 1Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, People’s Repu...

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Autores principales:	Han X, Tang S, Wang L, Xu X, Yan R, Yan S, Guo Z, Hu K, Yu T, Li M, Li Y, Zhang F, Gu N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	tunable mechanical properties dental pulp stem cells magnetic nanomaterials differentiation；multicellular spheroids Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ebe9ccb5ceb6400ab9150a2ea68aa1af
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spelling	oai:doaj.org-article:ebe9ccb5ceb6400ab9150a2ea68aa1af2021-12-02T15:06:16ZMulticellular Spheroids Formation on Hydrogel Enhances Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells Under Magnetic Nanoparticles Induction1178-2013https://doaj.org/article/ebe9ccb5ceb6400ab9150a2ea68aa1af2021-07-01T00:00:00Zhttps://www.dovepress.com/multicellular-spheroids-formation-on-hydrogel-enhances-osteogenicodont-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Xiao Han,1,2 Shijia Tang,1 Lin Wang,1 Xueqin Xu,2 Ruhan Yan,2 Sen Yan,3 Zhaobin Guo,4 Ke Hu,1,2 Tingting Yu,5 Mengping Li,2 Yuqin Li,2 Feimin Zhang,1,2 Ning Gu2,3 1Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Laboratory of Oral Regenerative Medicine Technology, School of Biomedical Engineering and Informatics, Department of Biomedical Engineering, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 4Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA; 5Department of Medical Genetics, School of Basic Medical Science & Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Feimin Zhang; Ning Gu Fax +86-25-86516414; +86-25-83272460Email fmzhang@njmu.edu.cn; guning@seu.edu.cnIntroduction: Promotion odontogenic differentiation of dental pulp stem cells (DPSCs) is essential for dentin regeneration. Physical cellular microenvironment is of critical importance for stem cells differentiation and influences the function of other biological/chemical factors to differentiation.Methods: Based on adjusting the mechanical/interfacial properties of hydrogels, multicellular spheroids (MCSs) of DPSCs generated through self-organization. The spheroids were characterized by immunofluorescent staining and flow cytometry. Quantitative real-time polymerase chain reaction, alkaline phosphatase (ALP) activity assay, ALP staining and Alizarin Red S staining were performed to evaluate the osteogenic/odontogenic differentiation of DPSCs with or without magnetic iron oxide nanoparticles (IONPs) induction.Results: MCSs of DPSCs exhibited a significant upregulation of E-cadherin and N-cadherin and enriched CD146 positive subpopulation, along with a stronger osteogenic/odontogenic differentiation ability. Moreover, DPSCs spheroids showed more substantial osteogenic differentiation tendency than the classical two-dimensional cultured DPSCs under the stimulation of magnetic IONPs.Conclusion: Three-dimensional spheroids culture of DPSCs based on composite viscoelastic materials combined with mechanical/magnetic stimulation may provide a theoretical basis for the subsequent development of dentin or bone regeneration technology.Keywords: tunable mechanical properties, dental pulp stem cells, magnetic nanomaterials, osteogenic/odontogenic differentiation, multicellular spheroidsHan XTang SWang LXu XYan RYan SGuo ZHu KYu TLi MLi YZhang FGu NDove Medical Pressarticletunable mechanical propertiesdental pulp stem cellsmagnetic nanomaterialsdifferentiation；multicellular spheroidsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 5101-5115 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tunable mechanical properties dental pulp stem cells magnetic nanomaterials differentiation；multicellular spheroids Medicine (General) R5-920
spellingShingle	tunable mechanical properties dental pulp stem cells magnetic nanomaterials differentiation；multicellular spheroids Medicine (General) R5-920 Han X Tang S Wang L Xu X Yan R Yan S Guo Z Hu K Yu T Li M Li Y Zhang F Gu N Multicellular Spheroids Formation on Hydrogel Enhances Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells Under Magnetic Nanoparticles Induction
description	Xiao Han,1,2 Shijia Tang,1 Lin Wang,1 Xueqin Xu,2 Ruhan Yan,2 Sen Yan,3 Zhaobin Guo,4 Ke Hu,1,2 Tingting Yu,5 Mengping Li,2 Yuqin Li,2 Feimin Zhang,1,2 Ning Gu2,3 1Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Laboratory of Oral Regenerative Medicine Technology, School of Biomedical Engineering and Informatics, Department of Biomedical Engineering, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 4Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA; 5Department of Medical Genetics, School of Basic Medical Science & Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Feimin Zhang; Ning Gu Fax +86-25-86516414; +86-25-83272460Email fmzhang@njmu.edu.cn; guning@seu.edu.cnIntroduction: Promotion odontogenic differentiation of dental pulp stem cells (DPSCs) is essential for dentin regeneration. Physical cellular microenvironment is of critical importance for stem cells differentiation and influences the function of other biological/chemical factors to differentiation.Methods: Based on adjusting the mechanical/interfacial properties of hydrogels, multicellular spheroids (MCSs) of DPSCs generated through self-organization. The spheroids were characterized by immunofluorescent staining and flow cytometry. Quantitative real-time polymerase chain reaction, alkaline phosphatase (ALP) activity assay, ALP staining and Alizarin Red S staining were performed to evaluate the osteogenic/odontogenic differentiation of DPSCs with or without magnetic iron oxide nanoparticles (IONPs) induction.Results: MCSs of DPSCs exhibited a significant upregulation of E-cadherin and N-cadherin and enriched CD146 positive subpopulation, along with a stronger osteogenic/odontogenic differentiation ability. Moreover, DPSCs spheroids showed more substantial osteogenic differentiation tendency than the classical two-dimensional cultured DPSCs under the stimulation of magnetic IONPs.Conclusion: Three-dimensional spheroids culture of DPSCs based on composite viscoelastic materials combined with mechanical/magnetic stimulation may provide a theoretical basis for the subsequent development of dentin or bone regeneration technology.Keywords: tunable mechanical properties, dental pulp stem cells, magnetic nanomaterials, osteogenic/odontogenic differentiation, multicellular spheroids
format	article
author	Han X Tang S Wang L Xu X Yan R Yan S Guo Z Hu K Yu T Li M Li Y Zhang F Gu N
author_facet	Han X Tang S Wang L Xu X Yan R Yan S Guo Z Hu K Yu T Li M Li Y Zhang F Gu N
author_sort	Han X
title	Multicellular Spheroids Formation on Hydrogel Enhances Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells Under Magnetic Nanoparticles Induction
title_short	Multicellular Spheroids Formation on Hydrogel Enhances Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells Under Magnetic Nanoparticles Induction
title_full	Multicellular Spheroids Formation on Hydrogel Enhances Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells Under Magnetic Nanoparticles Induction
title_fullStr	Multicellular Spheroids Formation on Hydrogel Enhances Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells Under Magnetic Nanoparticles Induction
title_full_unstemmed	Multicellular Spheroids Formation on Hydrogel Enhances Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells Under Magnetic Nanoparticles Induction
title_sort	multicellular spheroids formation on hydrogel enhances osteogenic/odontogenic differentiation of dental pulp stem cells under magnetic nanoparticles induction
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/ebe9ccb5ceb6400ab9150a2ea68aa1af
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_version_	1718388552463548416

Multicellular Spheroids Formation on Hydrogel Enhances Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells Under Magnetic Nanoparticles Induction

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