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开发一种用于鉴定间充质干细胞以提高生物安全性的新型基因表达谱。

Development of a novel gene expression panel for the characterization of MSCs for increased biological safety.

作者信息

Różycka-Baczyńska Anna M, Stepaniec Igor M, Warzycha Marta, Zdolińska-Malinowska Izabela, Oldak Tomasz, Rozwadowska Natalia, Kolanowski Tomasz J

机构信息

Research and Development Department, Polski Bank Komórek Macierzystych S.A. (FamiCord Group), Warsaw, Poland.

Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.

出版信息

J Appl Genet. 2024 Dec 2. doi: 10.1007/s13353-024-00917-5.

DOI:10.1007/s13353-024-00917-5
PMID:39621192
Abstract

Mesenchymal stromal cells (MSCs) have a wide range of therapeutic applications due to their multipotency, immunomodulatory, and anti-inflammatory properties. Their ability to migrate and recolonize damaged tissues is also remarkable. However, the controversial occurrence of spontaneous tumorigenesis or malignant transformation of MSCs raises concerns about proposed cell-based therapies for patients that researchers must address. There are several in vitro and in vivo strategies for MSC safety approval, but there is still no described coherent scheme that allows the assessment of MSC oncogenic potential in a simple, robust, and reproducible manner. Here, we have developed a diagnostic panel of molecular markers that allows for the accurate verification of the quality and safety of MSCs. Moreover, presented in this article diagnostic panel that can define the origin and tumorigenicity of MSCs can be easily introduced into the routine quality control processes of MSC-based product manufacturing which will improve further clinical applications of MSCs.

摘要

间充质基质细胞(MSCs)因其多能性、免疫调节和抗炎特性而具有广泛的治疗应用。它们迁移并重新定殖于受损组织的能力也很显著。然而,MSCs自发肿瘤发生或恶性转化这一有争议的现象引发了研究人员必须解决的对于针对患者的细胞疗法的担忧。有几种用于MSCs安全性批准的体外和体内策略,但仍然没有一种连贯的方案能够以简单、可靠且可重复的方式评估MSCs的致癌潜力。在此,我们开发了一组分子标志物诊断面板,可用于准确验证MSCs的质量和安全性。此外,本文介绍的能够定义MSCs起源和致瘤性的诊断面板可轻松引入基于MSCs的产品制造的常规质量控制流程,这将进一步改善MSCs的临床应用。

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本文引用的文献

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Clinical Trials Based on Mesenchymal Stromal Cells are Exponentially Increasing: Where are We in Recent Years?基于间充质基质细胞的临床试验呈指数级增长:近年来我们取得了哪些进展?
Stem Cell Rev Rep. 2022 Jan;18(1):23-36. doi: 10.1007/s12015-021-10231-w. Epub 2021 Aug 16.
2
Shattering barriers toward clinically meaningful MSC therapies.打破临床意义上 MSC 疗法的障碍。
Sci Adv. 2020 Jul 22;6(30):eaba6884. doi: 10.1126/sciadv.aba6884. eCollection 2020 Jul.
3
DNMT3B deficiency alters mitochondrial biogenesis and α-ketoglutarate levels in human embryonic stem cells.
DNMT3B 缺乏改变人胚胎干细胞中线粒体生物发生和 α-酮戊二酸水平。
Stem Cells. 2020 Nov;38(11):1409-1422. doi: 10.1002/stem.3256. Epub 2020 Jul 20.
4
The Multifaceted Roles of MSCs in the Tumor Microenvironment: Interactions With Immune Cells and Exploitation for Therapy.间充质干细胞在肿瘤微环境中的多方面作用:与免疫细胞的相互作用及治疗应用
Front Cell Dev Biol. 2020 Jun 19;8:447. doi: 10.3389/fcell.2020.00447. eCollection 2020.
5
The Interaction of CDH20 With β-Catenin Inhibits Cervical Cancer Cell Migration and Invasion via TGF-β/Smad/SNAIL Mediated EMT.CDH20与β-连环蛋白的相互作用通过TGF-β/Smad/SNAIL介导的上皮-间质转化抑制宫颈癌细胞的迁移和侵袭。
Front Oncol. 2020 Jan 9;9:1481. doi: 10.3389/fonc.2019.01481. eCollection 2019.
6
Mesenchymal stem cell perspective: cell biology to clinical progress.间充质干细胞展望:从细胞生物学到临床进展
NPJ Regen Med. 2019 Dec 2;4:22. doi: 10.1038/s41536-019-0083-6. eCollection 2019.
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Tumorigenicity assessment of cell therapy products: The need for global consensus and points to consider.细胞治疗产品的致瘤性评估:全球共识的必要性和需要考虑的要点。
Cytotherapy. 2019 Nov;21(11):1095-1111. doi: 10.1016/j.jcyt.2019.10.001. Epub 2019 Nov 9.
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IDO1 Maintains Pluripotency of Primed Human Embryonic Stem Cells by Promoting Glycolysis.IDO1 通过促进糖酵解来维持初始人类胚胎干细胞的多能性。
Stem Cells. 2019 Sep;37(9):1158-1165. doi: 10.1002/stem.3044. Epub 2019 Jun 10.
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Stem Cells. 2019 Feb;37(2):240-246. doi: 10.1002/stem.2934. Epub 2018 Nov 9.
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PLoS One. 2018 Oct 4;13(10):e0205022. doi: 10.1371/journal.pone.0205022. eCollection 2018.