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无注射剂递送 MSC 衍生的细胞外囊泡用于心肌梗死治疗。

Injection-Free Delivery of MSC-Derived Extracellular Vesicles for Myocardial Infarction Therapeutics.

机构信息

Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.

Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan, 450052, China.

出版信息

Adv Healthc Mater. 2022 Mar;11(5):e2100312. doi: 10.1002/adhm.202100312. Epub 2021 Jul 26.


DOI:10.1002/adhm.202100312
PMID:34310068
Abstract

As emerging therapeutic factors, extracellular vesicles (EVs) offer significant potential for myocardial infarction (MI) treatment. Current delivery approaches for EVs involve either intra-myocardial or intravenous injection, where both have inherent limitations for downstream clinical applications such as secondary tissue injury and low delivery efficiency. Herein, an injection-free approach for delivering EVs onto the heart surface to treat MI is proposed. By spraying a mixture of EVs, gelatin methacryloyl (GelMA) precursors, and photoinitiators followed by visible light irradiation for 30 s, EVs are physically entrapped within the GelMA hydrogel network covering the surface of the heart, resulting in an enhanced retention rate. Moreover, EVs are gradually released from the hydrogel network through a combination of diffusion and/or enzymatic degradation of the hydrogel, and they are effectively taken up by the sprayed tissue area. More importantly, the released EVs further migrate deep into myocardium tissue, which exerts an improved therapeutic effect. In an MI-induced mice model, the group treated with EVs-laden GelMA hydrogels shows significant recovery in cardiac function after 4 weeks. The work demonstrates a new strategy for delivering EVs into cardiac tissues for MI treatment in a localized manner with high retention.

摘要

作为新兴的治疗因子,细胞外囊泡 (EVs) 在心肌梗死 (MI) 治疗方面具有巨大的潜力。目前 EVs 的传递方法包括心肌内或静脉内注射,这两种方法都存在固有局限性,如二次组织损伤和低传递效率,不利于下游的临床应用。在此,提出了一种无需注射即可将 EVs 递送到心脏表面以治疗 MI 的方法。通过喷涂 EVs、明胶甲基丙烯酰 (GelMA) 前体和光引发剂的混合物,然后用可见光照射 30s,EVs 被物理包埋在覆盖心脏表面的 GelMA 水凝胶网络中,从而提高了保留率。此外,EVs 通过扩散和/或水凝胶的酶降解的组合从水凝胶网络中逐渐释放,并被喷涂组织区域有效吸收。更重要的是,释放的 EVs 进一步迁移到心肌组织深处,从而发挥更好的治疗效果。在 MI 诱导的小鼠模型中,用负载 EVs 的 GelMA 水凝胶治疗的组在 4 周后心脏功能显著恢复。该工作展示了一种新的策略,可将 EVs 局部递送到心脏组织中,以实现 MI 治疗的高保留率。

相似文献

[1]
Injection-Free Delivery of MSC-Derived Extracellular Vesicles for Myocardial Infarction Therapeutics.

Adv Healthc Mater. 2022-3

[2]
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Int J Mol Sci. 2022-1-13

[3]
VH298-loaded extracellular vesicles released from gelatin methacryloyl hydrogel facilitate diabetic wound healing by HIF-1α-mediated enhancement of angiogenesis.

Acta Biomater. 2022-7-15

[4]
Mesenchymal stem cell-derived extracellular vesicles alone or in conjunction with a SDKP-conjugated self-assembling peptide improve a rat model of myocardial infarction.

Biochem Biophys Res Commun. 2020-2-10

[5]
Gelatin Methacryloyl Bioadhesive Improves Survival and Reduces Scar Burden in a Mouse Model of Myocardial Infarction.

J Am Heart Assoc. 2020-6-2

[6]
Extracellular vesicles enriched with miR-150 released by macrophages regulates the TP53-IGF-1 axis to alleviate myocardial infarction.

Am J Physiol Heart Circ Physiol. 2021-3-1

[7]
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Theranostics. 2019-4-13

[8]
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Biomaterials. 2021-8

[9]
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J Biomed Mater Res A. 2022-6

[10]
Surface engineering enhances the therapeutic potential of systemically delivered extracellular vesicles following acute myocardial infarction.

FASEB J. 2024-9-30

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Mesenchymal stem cell-derived extracellular vesicles: current advances in preparation and therapeutic applications for neurological disorders.

Front Cell Dev Biol. 2025-8-18

[2]
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Tissue Eng Regen Med. 2025-6-5

[3]
Platelet Extracellular Vesicles as Natural Delivery Vehicles for Mitochondrial Dysfunction Therapy?

ACS Biomater Sci Eng. 2025-5-12

[4]
Injectable extracellular vesicle hydrogels with tunable viscoelasticity for depot vaccine.

Nat Commun. 2025-4-22

[5]
Microenvironmental Modulation for Therapeutic Efficacy of Extracellular Vesicles.

Adv Sci (Weinh). 2025-5

[6]
Combinational regenerative inductive effect of bio-adhesive hybrid hydrogels conjugated with hiPSC-derived myofibers and its derived EVs for volumetric muscle regeneration.

Bioact Mater. 2024-10-14

[7]
Injectable hydrogel with miR-222-engineered extracellular vesicles ameliorates myocardial ischemic reperfusion injury via mechanotransduction.

Cell Rep Med. 2025-3-18

[8]
Nucleic acid functionalized extracellular vesicles as promising therapeutic systems for nanomedicine.

Extracell Vesicles Circ Nucl Acids. 2022-2-22

[9]
Extracellular vesicle therapeutics for cardiac repair.

J Mol Cell Cardiol. 2025-2

[10]
Research hotspots and trends of mesenchymal stem cell-derived extracellular vesicles for drug delivery: a bibliometric and visualization analysis from 2013 to 2023.

Front Cell Dev Biol. 2024-10-30

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