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超越嵌合体分析:追踪新一代细胞疗法药物的方法

Beyond chimerism analysis: methods for tracking a new generation of cell-based medicines.

作者信息

Vives Joaquim, Casademont-Roca Aina, Martorell Lluís, Nogués Núria

机构信息

Servei de Teràpia Cel·lular, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005, Barcelona, Spain.

Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig de la Vall d'Hebron 129-139, 08035, Barcelona, Spain.

出版信息

Bone Marrow Transplant. 2020 Jul;55(7):1229-1239. doi: 10.1038/s41409-020-0822-8. Epub 2020 Feb 5.

DOI:10.1038/s41409-020-0822-8
PMID:32024991
Abstract

The analysis of chimerism is crucial to determine the status of patients receiving hematopoietic stem cell transplantation. The variety of relevant techniques available today range from those that analyse nucleic acids (i.e. polymerase chain reaction based, next generation sequencing) and cellular phenotype (i.e. flow cytometry) to sophisticated imaging (particularly multimodal imaging using labelling agents). However, current developments of advanced therapies bring chimerism studies into a new dimension in which methods for detection of donor cells in the patient need to adapt to a wider range of cell- and gene-based medicines, routes of administration, target organs and pathologies. Herein we describe and analyze the toolkit of suitable labelling and detection methodologies with actual examples along with a discussion on challenges ahead and potential solutions. Remarkably, existing methods commonly used in chimerism analysis are suitable for use with new cell- and gene-based medicines. Indeed, new developments may facilitate the evolution and combination of such methodologies to the use of non-invasive and highly informative approaches.

摘要

嵌合体分析对于确定接受造血干细胞移植患者的状况至关重要。当今可用的各种相关技术范围广泛,从分析核酸的技术(即基于聚合酶链反应的技术、下一代测序技术)和细胞表型分析技术(即流式细胞术)到复杂的成像技术(特别是使用标记剂的多模态成像技术)。然而,先进疗法的当前发展将嵌合体研究带入了一个新的维度,在这个维度中,检测患者体内供体细胞的方法需要适应更广泛的基于细胞和基因的药物、给药途径、靶器官和病理情况。在此,我们通过实际例子描述和分析合适的标记和检测方法工具包,并讨论未来面临的挑战和潜在解决方案。值得注意的是,嵌合体分析中常用的现有方法适用于新的基于细胞和基因的药物。事实上,新的发展可能会促进此类方法的演变和组合,以采用非侵入性且信息丰富的方法。

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New methods for the quantification of mixed chimerism in transplantation.移植中混合嵌合体定量的新方法。
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