Haematopoietic stem cell health in sickle cell disease and its implications for stem cell therapies and secondary haematological disorders

IF 6.9 2区 医学 Q1 HEMATOLOGY Blood Reviews Pub Date : 2024-01-01 DOI:10.1016/j.blre.2023.101137
Vishaka Gorur , Kamil R. Kranc , Miguel Ganuza , Paul Telfer
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Abstract

Gene modification of haematopoietic stem cells (HSCs) is a potentially curative approach to sickle cell disease (SCD) and offers hope for patients who are not eligible for allogeneic HSC transplantation. Current approaches require in vitro manipulation of healthy autologous HSC prior to their transplantation. However, the health and integrity of HSCs may be compromised by a variety of disease processes in SCD, and challenges have emerged in the clinical trials of gene therapy. There is also concern about increased susceptibility to haematological malignancies during long-term follow up of patients, and this raises questions about genomic stability in the stem cell compartment. In this review, we evaluate the evidence for HSC deficits in SCD and then discuss their potential causation. Finally, we suggest several questions which need to be addressed in order to progress with successful HSC manipulation for gene therapy in SCD.

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镰状细胞病的造血干细胞健康及其对干细胞治疗和继发性血液病的影响。
造血干细胞(HSC)的基因修饰是治疗镰状细胞病(SCD)的一种潜在方法,为不符合异基因造血干细胞移植条件的患者带来了希望。目前的方法需要在移植前对健康的自体造血干细胞进行体外操作。然而,造血干细胞的健康和完整性可能会受到SCD中各种疾病过程的影响,基因治疗的临床试验也出现了挑战。在患者的长期随访中,人们还担心对血液系统恶性肿瘤的易感性增加,这引发了对干细胞室基因组稳定性的质疑。在这篇综述中,我们评估了SCD中HSC缺陷的证据,然后讨论了它们的潜在原因。最后,我们提出了几个需要解决的问题,以便在SCD的基因治疗中成功地进行HSC操作。
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来源期刊
Blood Reviews
Blood Reviews 医学-血液学
CiteScore
13.80
自引率
1.40%
发文量
78
期刊介绍: Blood Reviews, a highly regarded international journal, serves as a vital information hub, offering comprehensive evaluations of clinical practices and research insights from esteemed experts. Specially commissioned, peer-reviewed articles authored by leading researchers and practitioners ensure extensive global coverage across all sub-specialties of hematology.
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