Immunomodulation by the combination of statin and matrix-bound nanovesicle enhances optic nerve regeneration.

IF 6.4 1区 医学 Q1 CELL & TISSUE ENGINEERING npj Regenerative Medicine Pub Date : 2024-10-26 DOI:10.1038/s41536-024-00374-y
Gregory P Campbell, Dwarkesh Amin, Kristin Hsieh, George S Hussey, Anthony J St Leger, Jeffrey M Gross, Stephen F Badylak, Takaaki Kuwajima
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Abstract

Modulating inflammation is critical to enhance nerve regeneration after injury. However, clinically applicable regenerative therapies that modulate inflammation have not yet been established. Here, we demonstrate synergistic effects of the combination of an HMG-CoA reductase inhibitor, statin/fluvastatin and critical components of the extracellular matrix, Matrix-Bound Nanovesicles (MBV) to enhance axon regeneration and neuroprotection after mouse optic nerve injury. Mechanistically, co-intravitreal injections of fluvastatin and MBV robustly promote infiltration of monocytes and neutrophils, which lead to RGC protection and axon regeneration. Furthermore, monocyte infiltration is triggered by elevated expression of CCL2, a chemokine, in the superficial layer of the retina after treatment with a combination of fluvastatin and MBV or IL-33, a cytokine contained within MBV. Finally, this therapy can be further combined with AAV-based gene therapy blocking anti-regenerative pathways in RGCs to extend regenerated axons. These data highlight novel molecular insights into the development of immunomodulatory regenerative therapy.

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他汀类药物与基质结合纳米颗粒的免疫调节作用可促进视神经再生。
调节炎症对促进损伤后的神经再生至关重要。然而,可用于临床的调节炎症的再生疗法尚未确立。在这里,我们展示了 HMG-CoA 还原酶抑制剂他汀/氟伐他汀与细胞外基质的关键成分--基质结合纳米颗粒(MBV)的协同作用,以增强小鼠视神经损伤后的轴突再生和神经保护。从机理上讲,联合静脉注射氟伐他汀和MBV能有力地促进单核细胞和中性粒细胞的浸润,从而促进RGC的保护和轴突再生。此外,在联合使用氟伐他汀和 MBV 或 MBV 所含的细胞因子 IL-33 治疗后,视网膜表层趋化因子 CCL2 的表达升高,也会引发单核细胞浸润。最后,这种疗法还可以进一步与基于 AAV 的基因疗法相结合,阻断 RGC 中的抗再生通路,从而延长再生轴突。这些数据凸显了开发免疫调节再生疗法的新分子见解。
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来源期刊
npj Regenerative Medicine
npj Regenerative Medicine Engineering-Biomedical Engineering
CiteScore
10.00
自引率
1.40%
发文量
71
审稿时长
12 weeks
期刊介绍: Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.
期刊最新文献
Peripheral nerve-derived CSF1 induces BMP2 expression in macrophages to promote nerve regeneration and wound healing. Heart regeneration from the whole-organism perspective to single-cell resolution. Systemic and local lipid adaptations underlie regeneration in Drosophila melanogaster and Ambystoma mexicanum. Regeneration-specific promoter switching facilitates Mest expression in the mouse digit tip to modulate neutrophil response. Immunomodulation by the combination of statin and matrix-bound nanovesicle enhances optic nerve regeneration.
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