Generation of red blood cells from stem cells: Achievements, opportunities and perspectives for malaria research.
Generation of red blood cells from stem cells: Achievements, opportunities and perspectives for malaria research.
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DOI：
10.3389/fcimb.2022.1039520
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发表时间：
2022
影响因子：
5.7
通讯作者：
Satchwell, Timothy J.
中科院分区：
文献类型：
--
作者：
Satchwell, Timothy J.
导致疟疾的疟原虫属寄生虫通过入侵并在体内增殖，体内最丰富的细胞类型--红细胞--在人体内生存。作为专性的细胞内寄生虫，寄生虫和宿主红细胞成分之间的相互作用对血液期疟疾寄生虫生命周期的多个方面至关重要。在寄生虫入侵和细胞内发育过程中，对一系列红细胞蛋白的需求和参与是很好的。然而，由于无核红细胞的遗传复杂性，对宿主细胞蛋白在这些过程中的作用的详细机制的了解受到阻碍。干细胞技术的出现，以及更具体地说，在体外重现称为红细胞生成的红细胞发育过程的方法的发展，使以前无法大量用于疟疾研究的红系细胞的产生成为可能。更重要的是，对有核红系前体进行基因操作的能力，可以分化为产生修饰的红细胞，这为疟疾研究开辟了新的视野。本文综述了目前利用干细胞的体外红系分化来产生对疟疾寄生虫入侵敏感的细胞的方法；讨论了现有的和新兴的产生新的红细胞表型的方法，并探索了体外衍生的红细胞的激发潜力，以更好地了解宿主红细胞蛋白在疟疾发病机制中的广泛作用。
Parasites of the genus Plasmodium that cause malaria survive within humans by invasion of, and proliferation within, the most abundant cell type in the body, the red blood cell. As obligate, intracellular parasites, interactions between parasite and host red blood cell components are crucial to multiple aspects of the blood stage malaria parasite lifecycle. The requirement for, and involvement of, an array of red blood cell proteins in parasite invasion and intracellular development is well established. Nevertheless, detailed mechanistic understanding of host cell protein contributions to these processes are hampered by the genetic intractability of the anucleate red blood cell. The advent of stem cell technology and more specifically development of methods that recapitulate in vitro the process of red blood cell development known as erythropoiesis has enabled the generation of erythroid cell stages previously inaccessible in large numbers for malaria studies. What is more, the capacity for genetic manipulation of nucleated erythroid precursors that can be differentiated to generate modified red blood cells has opened new horizons for malaria research. This review summarises current methodologies that harness in vitro erythroid differentiation of stem cells for generation of cells that are susceptible to malaria parasite invasion; discusses existing and emerging approaches to generate novel red blood cell phenotypes and explores the exciting potential of in vitro derived red blood cells for improved understanding the broad role of host red blood cell proteins in malaria pathogenesis.
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