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Research Article

In vivo real-time monitoring delayed administration of M2 macrophages to enhance healing of tendon by NIR-II fluorescence imaging

Yuzhou Chen1,2,§, Mo Chen1,3,§, Chengxuan Yu1,§, Huizhu Li1, Liman Sai4, Nguyen T. K. Thanh5,6, Yueming Wang7, Yan Wo7, Jian Zhang1, Xing Yang8, Evgenii L. Guryev9, Andrei V. Zvyagin9, Hao De10, Min Tang11, Shiyi Chen1, Yunxia Li1( ), Yuefeng Hao8( ), Sijia Feng1( ), Jun Chen1( )
Sports Medicine Institute of Fudan University, Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
Department of Orthopedic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
Department of Physics, Shanghai Normal University, Shanghai 200234, China
Biophysics Group, Department of Physics and Astronomy, University College London, London WC1E 6BT, UK
UCL Healthcare Biomagnetic and Nanomaterials Laboratories, London W1S 4BS, UK
Department of Anatomy and Physiology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
Department of Orthopedics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215500, China
Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod 603950, Russia
Mathematical Institute, University of Oxford, Oxford OX2 6GG, UK
Institute of Natural Sciences, School of Mathematics, Shanghai Jiao Tong University, Shanghai 200240, China

§ Yuzhou Chen, Mo Chen, and Chengxuan Yu contributed equally to this work.

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Graphical Abstract

In this study, near-infrared (NIR-II) imaging revealed that the timing of macrophage administration in cell therapy significantly influences their behavior and retention in rotator cuff injury healing in mice. Delayed therapy improved healing outcomes by altering macrophage chemotaxis, emphasizing the importance of administration timing in reparative cell therapies.

Abstract

The administration time is a critical but long-neglected point in cell therapy based on macrophages because the incorrect time of macrophage administration could result in diverse outcomes regarding the same macrophage therapy. In this work, the second near-infrared (NIR-II) fluorescence imaging in vivo tracking of M2 macrophages during a pro-healing therapy in the mice model of rotator cuff injury revealed that the behavior of administrated macrophages was influenced by the timing of their administration. The delayed cell therapy (DCT) group had a longer retention time of injected M2 macrophages in the repairing tissue than that in the immediate cell therapy (ICT) group. Both Keller–Segel model and histological analysis further demonstrated that DCT altered the chemotaxis of M2 macrophages and improved the healing outcome of the repaired structure in comparison with ICT. Our results offer a possible explanation of previous conflicting results on reparative cell therapy and provoke reconsideration of the timing of these therapies.

Keywords

macrophagecell therapyNIR-IIin vivo imagingdelayed therapytendon healing

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Nano Research
Volume 17 Issue 5,
May 2024
Pages 4379-4390
DOI: 10.1007/s12274-023-6363-x
Cite this article:
Chen Y, Chen M, Yu C, et al. In vivo real-time monitoring delayed administration of M2 macrophages to enhance healing of tendon by NIR-II fluorescence imaging. Nano Research, 2024, 17(5): 4379-4390. https://doi.org/10.1007/s12274-023-6363-x
Topics:
Fluorescence imagingImmunologyInfrared imagingMacrophagesMedical imaging

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Received: 12 September 2023
Revised: 23 November 2023
Accepted: 23 November 2023
Published: 12 January 2024
© Tsinghua University Press 2023
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