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Nano Research 2022, 15(2): 1680-1690 https://doi.org/10.1007/s12274-021-3868-z
Research Article | Issue | Published: 12 October 2021

Exosome-mimicking nanovesicles derived from efficacy-potentiated stem cell membrane and secretome for regeneration of injured tissue

Show Author's Information Chunxiao Qi§,  Xiangsheng Liu§,  Dengke Zhi§,  Yifan Tai,  Yufei Liu,  Qiqi Sun,  Kai Wang,  Shufang Wang( ),  Adam C. Midgley( ),  Deling Kong( )
Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China

Keywords:
regenerative medicine, acellular therapy, biomimetic nanovesicles, acute liver injury, hindlimb ischemia
Topics:
Cell engineering
An erratum to this article is available online at https://doi.org/10.1007/s12274-022-4483-3
Cite this article:
Qi C, Liu X, Zhi D, et al. Exosome-mimicking nanovesicles derived from efficacy-potentiated stem cell membrane and secretome for regeneration of injured tissue. Nano Research, 2022, 15(2): 1680-1690. https://doi.org/10.1007/s12274-021-3868-z
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Abstract Full text Electronic supplementary material About this article

Translation of exosome-based therapies to pharmaceutical use is hindered by difficulties in large-scale and cost-effective production of clinical-grade exosomes. The rational design of nanovesicles that mimic the functionalities and physicochemical properties of exosomes may circumvent these issues. In this study, membranes and secretome from efficacy-potentiated mesenchymal stem cells (MSCs) were developed into size-controllable nanovesicles (Meseomes). MSCs were primed with interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα), harvested, and exosome-mimicking Meseomes were subsequently synthesized via one-step extrusion. Meseomes demonstrated significant enhancement of pro-angiogenic, pro-proliferative, anti-inflammatory, and anti-fibrotic effects on endothelial cells, macrophages, and hepatic stellate cells in vitro. Meseomes from primed MSCs benefited from an enrichment of bioactive and therapeutic molecules compared to nanovesicles from unprimed MSCs, as validated by liquid chromatography–mass spectrometry (LC-MS) proteomic analysis. Systemic administration of Meseomes to acute liver injury models resulted in the recovery of liver function, attenuated tissue necrosis. Further assessment of locally administered Meseomes in acute hindlimb ischemia models resulted in the salvage of the majority of the ischemic hindlimb (> 80%), which was due to enhanced angiogenesis and M2 macrophage polarization. The versatility and therapeutic efficacy of our developed acellular Meseomes offer an appealing alternative to traditional cell or exosome therapies for regenerative and translational medicine.


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Abstract
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Electronic supplementary material
About this article

Exosome-mimicking nanovesicles derived from efficacy-potentiated stem cell membrane and secretome for regeneration of injured tissue

Show Author's information Chunxiao Qi§, Xiangsheng Liu§, Dengke Zhi§, Yifan Tai, Yufei Liu, Qiqi Sun, Kai Wang, Shufang Wang( ), Adam C. Midgley( ), Deling Kong( )
Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China

Abstract

Translation of exosome-based therapies to pharmaceutical use is hindered by difficulties in large-scale and cost-effective production of clinical-grade exosomes. The rational design of nanovesicles that mimic the functionalities and physicochemical properties of exosomes may circumvent these issues. In this study, membranes and secretome from efficacy-potentiated mesenchymal stem cells (MSCs) were developed into size-controllable nanovesicles (Meseomes). MSCs were primed with interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα), harvested, and exosome-mimicking Meseomes were subsequently synthesized via one-step extrusion. Meseomes demonstrated significant enhancement of pro-angiogenic, pro-proliferative, anti-inflammatory, and anti-fibrotic effects on endothelial cells, macrophages, and hepatic stellate cells in vitro. Meseomes from primed MSCs benefited from an enrichment of bioactive and therapeutic molecules compared to nanovesicles from unprimed MSCs, as validated by liquid chromatography–mass spectrometry (LC-MS) proteomic analysis. Systemic administration of Meseomes to acute liver injury models resulted in the recovery of liver function, attenuated tissue necrosis. Further assessment of locally administered Meseomes in acute hindlimb ischemia models resulted in the salvage of the majority of the ischemic hindlimb (> 80%), which was due to enhanced angiogenesis and M2 macrophage polarization. The versatility and therapeutic efficacy of our developed acellular Meseomes offer an appealing alternative to traditional cell or exosome therapies for regenerative and translational medicine.

Keywords: regenerative medicine, acellular therapy, biomimetic nanovesicles, acute liver injury, hindlimb ischemia

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Publication history
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Acknowledgements

Publication history

Received: 02 July 2021
Revised: 30 August 2021
Accepted: 04 September 2021
Published: 12 October 2021
Issue date: February 2022

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2021

Acknowledgements

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (NSFC) projects (Nos. 81901905, 81830060, and 82050410449) and China Postdoctoral Science Foundation (No. 2019M660989).

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