• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

符合药品生产质量管理规范（GMP）的无血清培养可保留人间充质基质细胞来源细胞外囊泡的治疗潜力。

GMP-compliant, serum-free cultures preserve therapeutic potential of extracellular vesicles from human mesenchymal stromal cells.

作者信息

Calascibetta Filippo, Martorana Annalisa, Lo Pinto Margot, Carcione Claudia, D'Arpa Salvatore, Amico Giandomenico, Miceli Vitale, Cuscino Nicola, Iannolo Gioacchin, Volpe Lorenzo, Scilabra Simone Dario, Conaldi Pier Giulio, Chinnici Cinzia Maria

机构信息

Regenerative Medicine Unit, Ri.MED Foundation, Palermo, Italy.

Proteomics Group, Ri.MED Foundation, Palermo, Italy.

出版信息

Front Cell Dev Biol. 2025 Sep 1;13:1633912. doi: 10.3389/fcell.2025.1633912. eCollection 2025.

DOI:10.3389/fcell.2025.1633912
PMID:40959666
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12434029/
Abstract

The therapeutic potential of extracellular vesicles (EVs) derived from human mesenchymal stromal cells (MSCs) is limited by the lack of standardized, Good Manufacturing Practice (GMP)-compliant production protocols. This study investigates the effects of MSC-Brew, a commercially available GMP-grade medium, on MSC-derived EVs in comparison to those produced in conventional cultures with DMEM supplemented with 10% fetal bovine serum (FBS). MSCs from adult dermis were successfully isolated and expanded in Brew medium while retaining their characteristic surface marker expression. MSC-EVs derived from Brew cultures met the Minimal Information for Studies of Extracellular Vesicles (MISEV) criteria, including particle size, concentration, marker expression, and minimal inflammatory cytokine content. Notably, Brew-EVs exhibited a significantly higher particle-to-protein ratio compared to EVs produced in FBS-containing cultures, indicating improved purity. Proteomic analysis revealed a largely conserved composition between Brew-EVs and conventionally produced EVs, and microRNA (miRNA) profiling identified only four differentially expressed miRNAs. Brew-EVs were enriched in anti-fibrotic miRNAs and effectively reduced collagen secretion in transforming growth factor (TGF)-β1-activated LX-2 cells, a human hepatic stellate cell line used as a model of liver fibrosis. These findings support MSC-Brew medium as a standardized, serum-free platform for the consistent production of high-quality EVs suitable for therapeutic applications.

摘要

源自人间充质基质细胞（MSC）的细胞外囊泡（EV）的治疗潜力受到缺乏标准化的、符合药品生产质量管理规范（GMP）的生产方案的限制。本研究调查了市售的GMP级培养基MSC-Brew对MSC衍生的EV的影响，并将其与在补充有10%胎牛血清（FBS）的DMEM常规培养物中产生的EV进行比较。来自成人真皮的MSC在Brew培养基中成功分离并扩增，同时保留其特征性表面标志物表达。源自Brew培养物的MSC-EV符合细胞外囊泡研究的最低信息（MISEV）标准，包括粒径、浓度、标志物表达和最低炎症细胞因子含量。值得注意的是，与含FBS培养物中产生的EV相比，Brew-EV表现出显著更高的颗粒与蛋白质比率，表明纯度提高。蛋白质组学分析揭示了Brew-EV与传统生产的EV之间在很大程度上保守的组成，并且微小RNA（miRNA）谱分析仅鉴定出四种差异表达的miRNA。Brew-EV富含抗纤维化miRNA，并有效降低转化生长因子（TGF）-β1激活的LX-2细胞（一种用作肝纤维化模型的人肝星状细胞系）中的胶原蛋白分泌。这些发现支持将MSC-Brew培养基作为一个标准化的无血清平台，用于持续生产适合治疗应用的高质量EV。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/814afc380efb/fcell-13-1633912-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/079493f9baa7/fcell-13-1633912-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/f8c39f8d7bae/fcell-13-1633912-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/98493dc0e074/fcell-13-1633912-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/b51290b7d1f0/fcell-13-1633912-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/5db52e5dee14/fcell-13-1633912-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/756a35722cb6/fcell-13-1633912-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/814afc380efb/fcell-13-1633912-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/079493f9baa7/fcell-13-1633912-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/f8c39f8d7bae/fcell-13-1633912-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/98493dc0e074/fcell-13-1633912-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/b51290b7d1f0/fcell-13-1633912-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/5db52e5dee14/fcell-13-1633912-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/756a35722cb6/fcell-13-1633912-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/12434029/814afc380efb/fcell-13-1633912-g007.jpg

相似文献

1
GMP-compliant, serum-free cultures preserve therapeutic potential of extracellular vesicles from human mesenchymal stromal cells.符合药品生产质量管理规范（GMP）的无血清培养可保留人间充质基质细胞来源细胞外囊泡的治疗潜力。
Front Cell Dev Biol. 2025 Sep 1;13:1633912. doi: 10.3389/fcell.2025.1633912. eCollection 2025.
2
In-vitro immunomodulatory efficacy of extracellular vesicles derived from TGF-β1/IFN-γ dual licensed human bone marrow mesenchymal stromal cells.转化生长因子-β1/干扰素-γ双许可的人骨髓间充质基质细胞衍生的细胞外囊泡的体外免疫调节功效
Stem Cell Res Ther. 2025 Jul 9;16(1):357. doi: 10.1186/s13287-025-04476-2.
3
Extracellular vesicles derived from clonal mesenchymal stromal cells preconditioned by indirect hypoxia modulate immune responses in diabetic mice more effectively than directly preconditioned vesicles.与直接预处理的囊泡相比，由间接缺氧预处理的克隆间充质基质细胞衍生的细胞外囊泡能更有效地调节糖尿病小鼠的免疫反应。
Stem Cell Res Ther. 2025 Aug 26;16(1):458. doi: 10.1186/s13287-025-04568-z.
4
Xeno-free cultured mesenchymal stromal cells release extracellular vesicles with a "therapeutic" miRNA cargo ameliorating cartilage inflammation .无血清培养的间充质基质细胞释放含有“治疗”miRNA 货物的细胞外囊泡，可改善软骨炎症。
Theranostics. 2023 Mar 5;13(5):1470-1489. doi: 10.7150/thno.77597. eCollection 2023.
5
[Influence and mechanism of extracellular vesicles derived from human dermal papilla cells on skin fibrosis in mice].[人真皮乳头细胞来源的细胞外囊泡对小鼠皮肤纤维化的影响及机制]
Zhonghua Shao Shang Yu Chuang Mian Xiu Fu Za Zhi. 2025 Jun 20;41(6):559-568. doi: 10.3760/cma.j.cn501225-20240925-00348.
6
Extracellular vesicles isolated from adipose tissue-derived mesenchymal stromal cells as carriers for Paclitaxel delivery.从脂肪组织来源的间充质基质细胞中分离的细胞外囊泡作为紫杉醇递送载体。
Stem Cell Res Ther. 2025 Jun 15;16(1):307. doi: 10.1186/s13287-025-04435-x.
7
MicroRNA-4516 in extracellular vesicles-derived mesenchymal stem cells suppressed integrin αV-mediated lung fibrosis.细胞外囊泡来源的间充质干细胞中的微小RNA-4516抑制整合素αV介导的肺纤维化。
Stem Cell Res Ther. 2025 Aug 15;16(1):442. doi: 10.1186/s13287-025-04559-0.
8
Culture of Hoffa fat pad mesenchymal stem/stromal cells on microcarrier suspension in vertical wheel bioreactor for extracellular vesicle production.在垂直轮生物反应器中，利用微载体悬浮培养 Hoffa 脂肪垫间充质干细胞/基质细胞，用于细胞外囊泡的生产。
Stem Cell Res Ther. 2024 Mar 5;15(1):61. doi: 10.1186/s13287-024-03681-9.
9
Extracellular Vesicles from Mesenchymal Stromal Cells Modulate Inflammatory Responses on Feline Mixed Glia.间充质基质细胞来源的细胞外囊泡调节猫混合神经胶质细胞的炎症反应。
Stem Cells Dev. 2025 Aug;34(15-16):343-356. doi: 10.1089/scd.2025.0042. Epub 2025 Jul 4.
10
Human bone marrow mesenchymal stem cell-derived extracellular vesicles induce inverse dose-dependent anti-fibrotic effects in human myofibroblast cultures and bleomycin-injured mice with pulmonary fibrosis.人骨髓间充质干细胞衍生的细胞外囊泡在人肌成纤维细胞培养物和博来霉素损伤的肺纤维化小鼠中诱导剂量依赖性的抗纤维化作用。
Biomed Pharmacother. 2025 Sep;190:118370. doi: 10.1016/j.biopha.2025.118370. Epub 2025 Jul 21.

本文引用的文献

1
Optimizing mesenchymal stem cell therapy: from isolation to GMP-compliant expansion for clinical application.优化间充质干细胞疗法：从分离到符合药品生产质量管理规范的扩增以用于临床应用
BMC Mol Cell Biol. 2025 May 6;26(1):15. doi: 10.1186/s12860-025-00539-7.
2
Minimum information for studies of extracellular vesicles (MISEV) as toolbox for rigorous, reproducible and homogeneous studies on extracellular vesicles.细胞外囊泡研究的最低限度信息（MISEV）：作为细胞外囊泡严格、可重复且统一研究的工具箱。
Toxicol In Vitro. 2025 Jun;106:106049. doi: 10.1016/j.tiv.2025.106049. Epub 2025 Mar 10.
3
Comprehensive Phenotyping of Extracellular Vesicles in Plasma of Healthy Humans - Insights Into Cellular Origin and Biological Variation.
健康人血浆中细胞外囊泡的综合表型分析——对细胞起源和生物学变异的见解
J Extracell Vesicles. 2025 Jan;14(1):e70039. doi: 10.1002/jev2.70039.
4
Nano-Delivery Revolution: Harnessing Mesenchymal Stem Cell-Derived Exosomes' Potential for Wound Healing.纳米递送革命：利用间充质干细胞衍生外泌体促进伤口愈合的潜力
Biomedicines. 2024 Dec 9;12(12):2791. doi: 10.3390/biomedicines12122791.
5
miRTarBase 2025: updates to the collection of experimentally validated microRNA-target interactions.miRTarBase 2025：经实验验证的微小RNA-靶标相互作用集合的更新
Nucleic Acids Res. 2025 Jan 6;53(D1):D147-D156. doi: 10.1093/nar/gkae1072.
6
Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Reversing Hepatic Fibrosis in 3D Liver Spheroids.间充质基质细胞衍生的细胞外囊泡用于逆转三维肝球体中的肝纤维化
Biomedicines. 2024 Aug 14;12(8):1849. doi: 10.3390/biomedicines12081849.
7
A Nonenzymatic Procedure to Obtain Human Mesenchymal Stromal Cells from the Dermis.一种从真皮中获得人基质间充质干细胞的非酶法程序。
Methods Mol Biol. 2024;2835:17-27. doi: 10.1007/978-1-0716-3995-5_2.
8
GMP-compliant manufacturing of biologically active cell-derived vesicles produced by extrusion technology.采用挤压技术符合药品生产质量管理规范（GMP）的生物活性细胞衍生囊泡的生产
J Extracell Biol. 2022 Dec 25;1(12):e70. doi: 10.1002/jex2.70. eCollection 2022 Dec.
9
Targeting thrombospondin-2 retards liver fibrosis by inhibiting TLR4-FAK/TGF-β signaling.靶向血小板反应蛋白-2通过抑制TLR4-FAK/TGF-β信号通路延缓肝纤维化。
JHEP Rep. 2024 Jan 24;6(3):101014. doi: 10.1016/j.jhepr.2024.101014. eCollection 2024 Mar.
10
Modulating the release of bioactive molecules of human mesenchymal stromal cell secretome: Heparinization of hyaluronic acid-based hydrogels.调控人间质基质细胞分泌组中生物活性分子的释放：基于透明质酸的水凝胶的肝素化。
Int J Pharm. 2024 Mar 25;653:123904. doi: 10.1016/j.ijpharm.2024.123904. Epub 2024 Feb 12.