Browsing by Author "Zhu, Dashuai"

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    Exosome-eluting stents for vascular healing after ischaemic injury.
    (Nature biomedical engineering, 2021-10) Hu, Shiqi; Li, Zhenhua; Shen, Deliang; Zhu, Dashuai; Huang, Ke; Su, Teng; Dinh, Phuong-Uyen; Cores, Jhon; Cheng, Ke
    Drug-eluting stents implanted after ischaemic injury reduce the proliferation of endothelial cells and vascular smooth muscle cells and thus neointimal hyperplasia. However, the eluted drug also slows down the re-endothelialization process, delays arterial healing and can increase the risk of late restenosis. Here we show that stents releasing exosomes derived from mesenchymal stem cells in the presence of reactive oxygen species enhance vascular healing in rats with renal ischaemia-reperfusion injury, promoting endothelial cell tube formation and proliferation, and impairing the migration of smooth muscle cells. Compared with drug-eluting stents and bare-metal stents, the exosome-coated stents accelerated re-endothelialization and decreased in-stent restenosis 28 days after implantation. We also show that exosome-eluting stents implanted in the abdominal aorta of rats with unilateral hindlimb ischaemia regulated macrophage polarization, reduced local vascular and systemic inflammation, and promoted muscle tissue repair.
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    Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine.
    (Nature biomedical engineering, 2022-07-04) Wang, Zhenzhen; Popowski, Kristen D; Zhu, Dashuai; de Juan Abad, Blanca López; Wang, Xianyun; Liu, Mengrui; Lutz, Halle; De Naeyer, Nicole; DeMarco, C Todd; Denny, Thomas N; Dinh, Phuong-Uyen C; Li, Zhenhua; Cheng, Ke
    The first two mRNA vaccines against infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that were approved by regulators require a cold chain and were designed to elicit systemic immunity via intramuscular injection. Here we report the design and preclinical testing of an inhalable virus-like-particle as a COVID-19 vaccine that, after lyophilisation, is stable at room temperature for over three months. The vaccine consists of a recombinant SARS-CoV-2 receptor-binding domain (RBD) conjugated to lung-derived exosomes which, with respect to liposomes, enhance the retention of the RBD in both the mucus-lined respiratory airway and in lung parenchyma. In mice, the vaccine elicited RBD-specific IgG antibodies, mucosal IgA responses and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile in the animals' lungs, and cleared them of SARS-CoV-2 pseudovirus after a challenge. In hamsters, two doses of the vaccine attenuated severe pneumonia and reduced inflammatory infiltrates after a challenge with live SARS-CoV-2. Inhalable and room-temperature-stable virus-like particles may become promising vaccine candidates.
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    Platelet membrane and stem cell exosome hybrids enhance cellular uptake and targeting to heart injury
    (Nano Today, 2021-08-01) Hu, Shiqi; Wang, Xianyun; Li, Zhenhua; Zhu, Dashuai; Cores, Jhon; Wang, Zhenzhen; Li, Junlang; Mei, Xuan; Cheng, Xiao; Su, Teng; Cheng, Ke
    Exosomes from mesenchymal stem cells have been widely studied as therapeutics to treat myocardial infarction. However, exosomes injected for therapeutic purposes face a number of challenges, including competition from endogenous exosomes, and the internalization/clearance by the mononuclear phagocyte system. There is also a lack of targeting. In this study, we hybridized stem cell-derived exosomes with platelet membranes to enhance their ability to target the injured heart and to reduce uptake by macrophages. Furthermore, we found that hybridization with platelet membranes induces macropinocytosis, enhancing the cellular uptake of exosomes by endothelial cells and cardiomyocytes drastically. In vivo studies showed the cardiac targeting ability of hybrid exosomes in a mouse model of myocardial infarction injury. Lastly, we determined cardiac functions and performed immunohistochemistry to confirm an enahnced therapeutic potency of platelet membrane modified exosomes as compared to non-modified exosomes. Our studies provide proof-of-concept data and a universal approach to enhance the binding and accumulation of exosomes in injured tissues.
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    Publisher Correction: Exosome-eluting stents for vascular healing after ischaemic injury.
    (Nature biomedical engineering, 2021-10) Hu, Shiqi; Li, Zhenhua; Shen, Deliang; Zhu, Dashuai; Huang, Ke; Su, Teng; Dinh, Phuong-Uyen; Cores, Jhon; Cheng, Ke
    The wrong Reporting Summary file was originally published for this Article; it has now been replaced with the correct file.