Sustained release of canine mesenchymal stem/stromal cell-derived extracellular vesicles rescues motor function in rodent spinal cord injury models

IF 3.4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy Pub Date : 2025-06-12 DOI:10.1016/j.reth.2025.05.014

Hidetaka Nishida , Haruhi Matsuura , Karin Yoshizaki , Yusuke Sakaguchi , Takeshi Izawa , Hikaru Sonoda , Kazuya Edamura , Yasuhiko Tabata

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引用次数: 0

Abstract

Introduction

Extracellular vesicles (EVs) are expected to be a novel promotes in regenerative therapy. EVs derived from canine mesenchymal stromal/stem cells (MSCs) have been shown to play an important role in tissue repair. For clinical application of EV therapy, a major challenge is to find scalable methods for EV collection and to facilitate continuing local EV action. The aim of this study is to develop collection methods for EVs derived from canine MSCs using anion exchange chromatography (AEX), and to determine the therapeutic effects of sustained release of EVs from cationized gelatin hydrogels in rats with spinal cord injury (SCI).

Methods

Canine MSC-derived EVs were isolated from the culture supernatant by AEX. Lipopolysaccharide-stimulated BV-2 cells were used to determine the immunomodulatory effect of EVs. Distinct cross-linked cationized gelatin hydrogels were created by thermal dehydration. The amount of EVs captured by and released from hydrogels were measured using ELISA for CD63. The effects of sustained release of EVs on SCI in rats were evaluated via motor function and cavity volume.

Results

EVs were collected from the culture supernatant of canine MSCs using AEX. Canine MSC derived EVs collected by AEX significantly reduced the expression levels of IL-1β and IL-6 in BV-2 cells induced by LPS. Sustained release of EVs from cationized hydrogels led to significant improvement of locomotion in SCI rats relative to the control group at 14- and 28-days post-injury. Cavity formation in the spinal cord with sustained release of EVs was significantly less than in the control group.

Conclusions

Canine MSC derived EVs cultured in serum-free medium using AEX were successfully collected. Sustained release of canine MSC derived EVs suppresses cavity formation in the spinal cord after SCI and promotes improvement in motor function.

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犬间充质干细胞/基质细胞来源的细胞外囊泡的持续释放可恢复啮齿动物脊髓损伤模型的运动功能

细胞外囊泡（EVs）有望在再生治疗中成为一种新的促进剂。来源于犬间充质基质/干细胞（MSCs）的ev已被证明在组织修复中发挥重要作用。对于EV治疗的临床应用，一个主要的挑战是找到可扩展的EV收集方法，并促进持续的局部EV作用。本研究的目的是利用阴离子交换色谱法（AEX）建立犬间充质干细胞中ev的收集方法，并确定阳离子明胶水凝胶中ev的缓释对脊髓损伤大鼠的治疗作用。方法采用AEX法从培养上清液中分离出扫描型msc衍生的ev。采用脂多糖刺激BV-2细胞测定ev的免疫调节作用。热脱水制备了不同交联阳离子明胶水凝胶。采用CD63酶联免疫吸附试验测定水凝胶捕获和释放的电动汽车数量。通过运动功能和空腔容积评价ev缓释对大鼠脊髓损伤的影响。结果用AEX法从犬间充质干细胞培养上清中收集到v。AEX收集的犬MSC衍生ev显著降低LPS诱导的BV-2细胞中IL-1β和IL-6的表达水平。在损伤后14天和28天，与对照组相比，从阳离子水凝胶中持续释放ev可显著改善脊髓损伤大鼠的运动能力。与对照组相比，ev持续释放组脊髓空腔形成明显减少。结论用AEX在无血清培养基中成功培养了MSC衍生的ev。持续释放犬间充质干细胞衍生的ev可抑制脊髓损伤后脊髓腔的形成，促进运动功能的改善。

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来源期刊

Regenerative Therapy Engineering-Biomedical Engineering

CiteScore

6.00

自引率

2.30%

发文量

106

审稿时长

49 days

期刊介绍： Regenerative Therapy is the official peer-reviewed online journal of the Japanese Society for Regenerative Medicine. Regenerative Therapy is a multidisciplinary journal that publishes original articles and reviews of basic research, clinical translation, industrial development, and regulatory issues focusing on stem cell biology, tissue engineering, and regenerative medicine.