Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, Barcelona, Spain.
Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain.
Stem Cells Transl Med. 2022 Nov 18;11(11):1123-1134. doi: 10.1093/stcltm/szac071.
Several decades have passed since the generation of the first embryonic stem cell (ESC) lines both in mice and in humans. Since then, stem cell biologists have tried to understand their potential biological and clinical uses for their implementation in regenerative medicine. The hematopoietic field was a pioneer in establishing the potential use for the development of blood cell products and clinical applications; however, early expectations have been truncated by the difficulty in generating bonafide hematopoietic stem cells (HSCs). Despite some progress in understanding the origin of HSCs during embryonic development, the reproduction of this process in vitro is still not possible, but the knowledge acquired in the embryo is slowly being implemented for mouse and human pluripotent stem cells (PSCs). In contrast, ESC-derived hematopoietic cells may recapitulate some leukemic transformation processes when exposed to oncogenic drivers. This would be especially useful to model prenatal leukemia development or other leukemia-predisposing syndromes, which are difficult to study. In this review, we will review the state of the art of the use of PSCs as a model for hematopoietic and leukemia development.
几十年来，无论是在小鼠还是人类中，第一代胚胎干细胞 (ESC) 系的产生都已经过去了。从那时起，干细胞生物学家就一直在努力探索它们在再生医学中的潜在生物学和临床用途。造血领域是率先确定其用于血细胞产品开发和临床应用潜力的领域；然而，由于难以产生真正的造血干细胞 (HSC)，早期的预期受到了限制。尽管在理解胚胎发育过程中 HSC 的起源方面取得了一些进展，但在体外复制这一过程仍然是不可能的，但在胚胎中获得的知识正在缓慢地应用于小鼠和人类多能干细胞 (PSC)。相比之下，当暴露于致癌驱动因子时，ESC 衍生的造血细胞可能会再现一些白血病转化过程。这对于模拟产前白血病发展或其他易患白血病的综合征特别有用，因为这些综合征很难研究。在这篇综述中，我们将回顾使用 PSC 作为造血和白血病发展模型的最新技术状态。
