Dynamic three-dimensional culture enhances tunneling nanotubes-mediated mitochondrial transfer in mesenchymal stromal cells to accelerate wound healing
Abstract Mesenchymal stromal cells (MSCs) have shown promise in treating various diseases, and optimizing their therapeutic potential is a crucial objective in MSCs-based clinical applications. The microenvironment, particularly three-dimensional (3D) culture systems, plays a pivotal role in regulat...
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2025-08-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03655-w |
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| author | Lin Ma Xiaoxue Yang Xiaoyao Huang Hao Guo Zihan Li Siyuan Fan Han Qin Fanhui Meng Peisheng Liu Xinyu Wang Meiling Wu Kun Xuan Anqi Liu |
| author_facet | Lin Ma Xiaoxue Yang Xiaoyao Huang Hao Guo Zihan Li Siyuan Fan Han Qin Fanhui Meng Peisheng Liu Xinyu Wang Meiling Wu Kun Xuan Anqi Liu |
| author_sort | Lin Ma |
| collection | DOAJ |
| description | Abstract Mesenchymal stromal cells (MSCs) have shown promise in treating various diseases, and optimizing their therapeutic potential is a crucial objective in MSCs-based clinical applications. The microenvironment, particularly three-dimensional (3D) culture systems, plays a pivotal role in regulating the fate determination and enhancing the therapeutic potential of MSCs. Currently, the mechanisms governing the interactions between MSCs cultured in a dynamic 3D system and host recipient cells remain incompletely understood. MSCs transfer mitochondria to influence the fate of recipient cells, with tunneling nanotubes (TNTs) being the primary method. However, whether MSCs cultured under dynamic 3D conditions transfer mitochondria via TNTs to exert therapeutic effects remains to be elucidated. This study developed a dynamic 3D culture system for stem cells from human exfoliated deciduous teeth (SHED), a type of MSCs, utilizing gelatin microcryogel microcarriers and stirred tank bioreactor. A mouse model of full-thickness skin defects was employed to validate the enhanced therapeutic efficacy of SHED cultured under dynamic 3D conditions. Co-culture experiments with SHED and endothelial cells demonstrated that the dynamic 3D culture conditions empower the MSCs to transfer mitochondria via TNTs, thereby promoting angiogenesis. This research provides novel insights into the mechanisms underlying wound healing acceleration by SHED cultured under dynamic 3D conditions and offers a new strategy for developing MSCs transplantation applications. Graphical abstract |
| format | Article |
| id | doaj-art-a3508f47facb468a9cf17dd8af96dba6 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | Journal of Nanobiotechnology |
| spelling | doaj-art-a3508f47facb468a9cf17dd8af96dba62025-08-20T03:42:52ZengBMCJournal of Nanobiotechnology1477-31552025-08-0123112010.1186/s12951-025-03655-wDynamic three-dimensional culture enhances tunneling nanotubes-mediated mitochondrial transfer in mesenchymal stromal cells to accelerate wound healingLin Ma0Xiaoxue Yang1Xiaoyao Huang2Hao Guo3Zihan Li4Siyuan Fan5Han Qin6Fanhui Meng7Peisheng Liu8Xinyu Wang9Meiling Wu10Kun Xuan11Anqi Liu12State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical UniversityThe Lianyungang Affiliated Hospital of Xuzhou Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical UniversityAbstract Mesenchymal stromal cells (MSCs) have shown promise in treating various diseases, and optimizing their therapeutic potential is a crucial objective in MSCs-based clinical applications. The microenvironment, particularly three-dimensional (3D) culture systems, plays a pivotal role in regulating the fate determination and enhancing the therapeutic potential of MSCs. Currently, the mechanisms governing the interactions between MSCs cultured in a dynamic 3D system and host recipient cells remain incompletely understood. MSCs transfer mitochondria to influence the fate of recipient cells, with tunneling nanotubes (TNTs) being the primary method. However, whether MSCs cultured under dynamic 3D conditions transfer mitochondria via TNTs to exert therapeutic effects remains to be elucidated. This study developed a dynamic 3D culture system for stem cells from human exfoliated deciduous teeth (SHED), a type of MSCs, utilizing gelatin microcryogel microcarriers and stirred tank bioreactor. A mouse model of full-thickness skin defects was employed to validate the enhanced therapeutic efficacy of SHED cultured under dynamic 3D conditions. Co-culture experiments with SHED and endothelial cells demonstrated that the dynamic 3D culture conditions empower the MSCs to transfer mitochondria via TNTs, thereby promoting angiogenesis. This research provides novel insights into the mechanisms underlying wound healing acceleration by SHED cultured under dynamic 3D conditions and offers a new strategy for developing MSCs transplantation applications. Graphical abstracthttps://doi.org/10.1186/s12951-025-03655-wThree-dimensional cultureMitochondrial transferMesenchymal stromal cellsWound healingTunneling nanotubesCell therapy |
| spellingShingle | Lin Ma Xiaoxue Yang Xiaoyao Huang Hao Guo Zihan Li Siyuan Fan Han Qin Fanhui Meng Peisheng Liu Xinyu Wang Meiling Wu Kun Xuan Anqi Liu Dynamic three-dimensional culture enhances tunneling nanotubes-mediated mitochondrial transfer in mesenchymal stromal cells to accelerate wound healing Journal of Nanobiotechnology Three-dimensional culture Mitochondrial transfer Mesenchymal stromal cells Wound healing Tunneling nanotubes Cell therapy |
| title | Dynamic three-dimensional culture enhances tunneling nanotubes-mediated mitochondrial transfer in mesenchymal stromal cells to accelerate wound healing |
| title_full | Dynamic three-dimensional culture enhances tunneling nanotubes-mediated mitochondrial transfer in mesenchymal stromal cells to accelerate wound healing |
| title_fullStr | Dynamic three-dimensional culture enhances tunneling nanotubes-mediated mitochondrial transfer in mesenchymal stromal cells to accelerate wound healing |
| title_full_unstemmed | Dynamic three-dimensional culture enhances tunneling nanotubes-mediated mitochondrial transfer in mesenchymal stromal cells to accelerate wound healing |
| title_short | Dynamic three-dimensional culture enhances tunneling nanotubes-mediated mitochondrial transfer in mesenchymal stromal cells to accelerate wound healing |
| title_sort | dynamic three dimensional culture enhances tunneling nanotubes mediated mitochondrial transfer in mesenchymal stromal cells to accelerate wound healing |
| topic | Three-dimensional culture Mitochondrial transfer Mesenchymal stromal cells Wound healing Tunneling nanotubes Cell therapy |
| url | https://doi.org/10.1186/s12951-025-03655-w |
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