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.

中文翻译：

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超越嵌合体分析：跟踪新一代基于细胞的药物的方法。

嵌合分析对于确定接受造血干细胞移植的患者的状况至关重要。当今可用的各种相关技术，从分析核酸（即基于聚合酶链反应的下一代测序）和细胞表型（即流式细胞仪）的技术到复杂的成像（尤其是使用标记剂的多峰成像）。然而，当前先进疗法的发展将嵌合症研究带入了一个新的领域，在该领域中，用于检测患者中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，靶器官和病理学。在这里，我们将通过实际示例描述和分析适合的标记和检测方法的工具包，并讨论未来的挑战和潜在的解决方案。值得注意的是，嵌合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。确实，新的发展可能会促进这种方法的演变和组合，以使用非侵入性和高度信息化的方法。