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多孔微针贴片持续递送细胞外囊泡减轻严重脊髓损伤。

Porous microneedle patch with sustained delivery of extracellular vesicles mitigates severe spinal cord injury.

机构信息

Department of Rehabilitation Medicine of First Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, 310003, Hangzhou, Zhejiang Province, P. R. China.

Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, 1369 West Wenyi Road, 311121, Hangzhou, China.

出版信息

Nat Commun. 2023 Jul 7;14(1):4011. doi: 10.1038/s41467-023-39745-2.

Abstract

The transplantation of mesenchymal stem cells-derived secretome, particularly extracellular vesicles is a promising therapy to suppress spinal cord injury-triggered neuroinflammation. However, efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains a challenge. Here we present a device for the delivery of extracellular vesicles to treat spinal cord injury. We show that the device incorporating mesenchymal stem cells and porous microneedles enables the delivery of extracellular vesicles. We demonstrate that topical application to the spinal cord lesion beneath the spinal dura, does not damage the lesion. We evaluate the efficacy of our device in a contusive spinal cord injury model and find that it reduces the cavity and scar tissue formation, promotes angiogenesis, and improves survival of nearby tissues and axons. Importantly, the sustained delivery of extracellular vesicles for at least 7 days results in significant functional recovery. Thus, our device provides an efficient and sustained extracellular vesicles delivery platform for spinal cord injury treatment.

摘要

间充质干细胞来源的分泌组,特别是细胞外囊泡的移植,是一种有前途的抑制脊髓损伤引发的神经炎症的治疗方法。然而,将细胞外囊泡高效递送至受伤的脊髓,同时最小化损伤,仍然是一个挑战。在这里,我们提出了一种用于递送至治疗脊髓损伤的细胞外囊泡的装置。我们表明,包含间充质干细胞和多孔微针的装置能够递送细胞外囊泡。我们证明,将其施用于脊髓硬脑膜下的脊髓损伤部位,不会损伤损伤部位。我们在挫伤性脊髓损伤模型中评估了我们装置的疗效,发现它减少了空洞和疤痕组织的形成,促进了血管生成,并改善了周围组织和轴突的存活。重要的是,至少 7 天的持续细胞外囊泡递送导致了显著的功能恢复。因此,我们的装置为脊髓损伤治疗提供了一种高效和持续的细胞外囊泡递送平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7190/10328956/782a99c5ff53/41467_2023_39745_Fig1_HTML.jpg

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