Soares-da-Silva Francisca, Peixoto Márcia, Cumano Ana, Pinto-do-Ó Perpetua
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
Front Cell Dev Biol. 2020 Jul 22;8:612. doi: 10.3389/fcell.2020.00612. eCollection 2020.
Hematopoietic stem cells (HSCs) generated during embryonic development are able to maintain hematopoiesis for the lifetime, producing all mature blood lineages. HSC transplantation is a widely used cell therapy intervention in the treatment of hematologic, autoimmune and genetic disorders. Its use, however, is hampered by the inability to expand HSCs , urging for a better understanding of the mechanisms regulating their physiological expansion. In the adult, HSCs reside in the bone marrow, in specific microenvironments that support stem cell maintenance and differentiation. Conversely, while developing, HSCs are transiently present in the fetal liver, the major hematopoietic site in the embryo, where they expand. Deeper insights on the dynamics of fetal liver composition along development, and on how these different cell types impact hematopoiesis, are needed. Both, the hematopoietic and hepatic fetal systems have been extensively studied, albeit independently. This review aims to explore their concurrent establishment and evaluate to what degree they may cross modulate their respective development. As insights on the molecular networks that govern physiological HSC expansion accumulate, it is foreseeable that strategies to enhance HSC proliferation will be improved.
胚胎发育过程中产生的造血干细胞(HSCs)能够终生维持造血功能,产生所有成熟的血细胞谱系。造血干细胞移植是一种广泛应用于治疗血液学、自身免疫性和遗传性疾病的细胞治疗干预手段。然而,由于无法扩增造血干细胞,其应用受到了阻碍,这促使人们更好地了解调节其生理扩增的机制。在成体中,造血干细胞存在于骨髓中特定的微环境中,这些微环境支持干细胞的维持和分化。相反,在发育过程中,造血干细胞短暂存在于胚胎主要造血部位——胎儿肝脏中,并在那里扩增。需要更深入地了解胎儿肝脏组成随发育的动态变化,以及这些不同细胞类型如何影响造血功能。造血和肝脏胎儿系统都已得到广泛研究,尽管是独立进行的。本综述旨在探讨它们的同时建立,并评估它们在何种程度上可能相互交叉调节各自的发育。随着对控制生理造血干细胞扩增的分子网络的认识不断积累,可以预见,增强造血干细胞增殖的策略将会得到改进。