Extracellular vesicles isolated from adipose tissue-derived mesenchymal stromal cells as carriers for Paclitaxel delivery.

IF 7.1 2区 医学 Q1 CELL & TISSUE ENGINEERING
Angela Marcianti, Eleonora Spampinato, Sara Nava, Giulia Maria Stella, Paola Perego, Simona Pogliani, Simona Frigerio, Luca Mirra, Paola Gagni, Fabio Moda, Federico Angelo Cazzaniga, Giovanni Luca Beretta, Guido Maronati, Giuseppe Paglia, Angelo Guido Corsico, Catia Traversari, Daniela Lisini
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引用次数: 0

Abstract

Background: Mesenchymal Stromal Cells (MSC)-derived Extracellular Vesicles (EV) represent innovative tools for drug delivery systems. However, their clinical use is limited by the lack of standardized good manufacturing practice (GMP)-compliant isolation and conservation protocols. In this study, we developed a GMP-compliant protocol for the preparation of MSC-EVs and investigated the feasibility of producing EVs loaded with paclitaxel (PTX) for clinical application as drug products.

Methods: Adipose tissues from 13 donors were used to obtain MSC-EVs via culture supernatant ultracentrifugation. EVs loaded with PTX were manufactured by adding the drug to the culture medium of MSCs before supernatant collection. EV identity was verified in terms of concentration/size, protein content, morphology, and expression of EV surface markers. The anti-proliferative activity, accumulation ability in tumor cells and PTX content, as well as their stability over time, were also evaluated.

Results: High numbers of EV/EV-PTX compliant in terms of integrity/identity were obtained and can be successfully stored for up to one year at -80 °C. Cellular studies have shown that EVs are capable of accumulating in tumor cells and, when loaded with PTX, inhibiting the proliferation of a pleural mesothelioma cell line.

Conclusions: These results support the potential future clinical use of EVs as carriers for drug delivery to improve cancer treatment strategies.

从脂肪组织来源的间充质间质细胞分离的细胞外囊泡作为紫杉醇递送的载体。
背景:间充质基质细胞(MSC)衍生的细胞外囊泡(EV)是药物传递系统的创新工具。然而,由于缺乏符合GMP标准的分离和保存方案,它们的临床应用受到限制。在本研究中,我们制定了一个符合gmp的msc - ev制备方案,并研究了生产装载紫杉醇(PTX)的ev作为临床药物应用的可行性。方法:取13例供体脂肪组织,通过培养上清超离心获得MSC-EVs。在收集上清之前,将PTX加入MSCs的培养基中制备装载PTX的ev。从浓度/大小、蛋白质含量、形态和EV表面标记的表达等方面验证了EV的身份。并对其抗增殖活性、肿瘤细胞蓄积能力、PTX含量及其随时间的稳定性进行了评价。结果:获得了大量符合完整性/一致性的EV/EV- ptx,并可在-80°C下成功保存长达一年。细胞研究表明,ev能够在肿瘤细胞中积累,并且当装载PTX时,可以抑制胸膜间皮瘤细胞系的增殖。结论:这些结果支持了ev作为药物递送载体的潜在未来临床应用,以改善癌症治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Stem Cell Research & Therapy
Stem Cell Research & Therapy CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
13.20
自引率
8.00%
发文量
525
审稿时长
1 months
期刊介绍: Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.
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