Clifford Chao, Isabella G Martinez, Elvin Wagenblast
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New methods, including specialized mouse strains and human tissue scaffolds, have been developed to address these issues. Induced pluripotent stem cells (iPSCs) offer the advantage of indefinite expansion and genetic modification, making them valuable for in vitro research, though protocols to enhance their engraftment in vivo are still being refined. Genetically engineered human primary hematopoietic stem and progenitor cells (HSPCs) provide reliable in vivo models with good engraftment in mice, and recent advancements in culture systems and gene-editing techniques are helping to overcome challenges related to ex vivo expansion and genetic modification.</p><p><strong>Summary: </strong>PDXs, iPSCs, and genetically engineered HSPCs are crucial models for the study of MDS and AML. 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引用次数: 0
摘要
综述的目的:骨髓增生异常综合征(MDS)和急性髓性白血病(AML)是以复杂的基因改变为特征的血液恶性肿瘤,导致不良的临床预后。尽管在治疗方面取得了进展,但仍迫切需要新的治疗方法。本综述概述了 MDS 和 AML 人源化模型的最新进展,并强调了这些模型在促进我们对这些疾病的了解方面所起的作用:患者衍生异种移植物(PDX)是研究 MDS 和 AML 的首批人源化模型之一,使研究人员能够在体内分析患者特异性癌症特性。然而,它们面临着样本可用性和在小鼠体内稳定移植的挑战。为了解决这些问题,我们开发了新的方法,包括专门的小鼠品系和人体组织支架。诱导多能干细胞(iPSCs)具有无限期扩增和基因修饰的优势,因此对体外研究很有价值,但增强其体内移植的方案仍在完善中。基因工程人类原代造血干细胞和祖细胞(HSPCs)提供了可靠的体内模型,在小鼠体内具有良好的移植效果,最近在培养系统和基因编辑技术方面取得的进展有助于克服体内外扩增和基因修饰方面的挑战。摘要:PDXs、iPSCs 和基因工程 HSPCs 是研究 MDS 和 AML 的重要模型。这篇综述讨论了这些人源化模型的优势、局限性和最新进展,它们为人类特异性疾病生物学和治疗开发提供了见解。
Models to study myelodysplastic syndrome and acute myeloid leukaemia.
Purpose of review: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematological malignancies characterized by complex genetic alterations, leading to poor clinical outcomes. Despite advances in treatment, there is an urgent need for novel therapeutic approaches. This review outlines recent progress in humanized models of MDS and AML and highlight their role in advancing our understanding of these diseases.
Recent findings: Patient derived xenografts (PDXs) were among the first humanized models for studying MDS and AML, allowing researchers to analyze patient-specific cancer properties in vivo. However, they face challenges related to sample availability and consistent engraftment in mice. New methods, including specialized mouse strains and human tissue scaffolds, have been developed to address these issues. Induced pluripotent stem cells (iPSCs) offer the advantage of indefinite expansion and genetic modification, making them valuable for in vitro research, though protocols to enhance their engraftment in vivo are still being refined. Genetically engineered human primary hematopoietic stem and progenitor cells (HSPCs) provide reliable in vivo models with good engraftment in mice, and recent advancements in culture systems and gene-editing techniques are helping to overcome challenges related to ex vivo expansion and genetic modification.
Summary: PDXs, iPSCs, and genetically engineered HSPCs are crucial models for the study of MDS and AML. This review discusses strengths, limitations, and recent advancements of these humanized models, which provide insights into human-specific disease biology and therapeutic development.
期刊介绍:
Current Opinion in Hematology is an easy-to-digest bimonthly journal covering the most interesting and important advances in the field of hematology. Its hand-picked selection of editors ensure the highest quality selection of unbiased review articles on themes from nine key subject areas, including myeloid biology, Vascular biology, hematopoiesis and erythroid system and its diseases.