Fetal liver hematopoiesis: from development to delivery.

Fetal liver hematopoiesis: from development to delivery.
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DOI:
10.1186/s13287-021-02189-w
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发表时间:
2021-02-17
影响因子:
7.5
通讯作者:
Takebe T
Takebe T
中科院分区:
医学2区
文献类型:
--
作者:
Lewis K;Yoshimoto M;Takebe T

文献摘要

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临床移植的造血干细胞(HSC)可以为许多血液病提供一种挽救生命的治疗方法,但供者的可获得性阻碍了治疗应用。在体内,HSC存在于一个特定的微环境中,称为小生境。虽然大多数研究集中在骨髓(BM)中的干细胞,但更好地了解胚胎肝脏在发育过程中的生态位对于设计人类多能干细胞(PSC)培养至关重要,并可能为体外扩增供移植的HSC提供有价值的见解。这篇综述将讨论胎肝龛在HSC扩增中的重要性,这是一项发生在发育过程中的壮举,具有巨大的临床潜力。我们还将讨论在细胞培养中产生可扩展的HSC的新方法,这些方法结合工程和系统生物学方法以细胞或器官模型的形式获得更多的复杂性。总体而言,通过绘制发育原理来提供HSC将有助于理解HSC与胎肝细胞之间的分子和生物学相互作用,以实现其受控成熟和扩增。
Clinical transplants of hematopoietic stem cells (HSC) can provide a lifesaving therapy for many hematological diseases; however, therapeutic applications are hampered by donor availability. In vivo, HSC exist in a specified microenvironment called the niche. While most studies of the niche focus on those residing in the bone marrow (BM), a better understanding of the fetal liver niche during development is vital to design human pluripotent stem cell (PSC) culture and may provide valuable insights with regard to expanding HSCs ex vivo for transplantation. This review will discuss the importance of the fetal liver niche in HSC expansion, a feat that occurs during development and has great clinical potential. We will also discuss emerging approaches to generate expandable HSC in cell culture that attain more complexity in the form of cells or organoid models in combination with engineering and systems biology approaches. Overall, delivering HSC by charting developmental principles will help in the understanding of the molecular and biological interactions between HSCs and fetal liver cells for their controlled maturation and expansion.