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.

中文翻译：

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胎儿肝脏造血：从发育到分娩


造血干细胞（HSC）的临床移植可以为许多血液疾病提供挽救生命的治疗方法；然而，治疗应用受到捐助者可用性的阻碍。在体内，HSC存在于称为生态位的特定微环境中。虽然大多数关于该生态位的研究都集中在那些存在于骨髓 (BM) 中的生态位，但更好地了解发育过程中的胎儿肝脏生态位对于设计人类多能干细胞 (PSC) 培养物至关重要，并且可能为扩展 HSC 提供有价值的见解离体移植。这篇综述将讨论胎儿肝脏生态位在 HSC 扩增中的重要性，这是在发育过程中发生的一项壮举，具有巨大的临床潜力。我们还将讨论在细胞培养中生成可扩展 HSC 的新兴方法，这些方法结合工程和系统生物学方法，以细胞或类器官模型的形式获得更复杂的结果。总体而言，通过绘制发育原理来提供 HSC 将有助于理解 HSC 与胎儿肝细胞之间的分子和生物相互作用，以控制其成熟和扩张。