德国汉诺威医学院Robert Zweigerdt等合作取得一项新成果。他们开发产生血液的心脏形成类器官，重现了人类造血系统和胚胎心脏的共同发育。这一研究成果发表在2024年10月8日出版的国际学术期刊《自然—生物技术》上。

据悉，尽管造血干细胞和造血祖细胞具有重要的生物医学意义，但由于对指定多种造血波的信号和标记的知识有限，以及对人类胚胎的伦理限制，它们在发育背景下的体外稳定尚未实现。因此，在体外模拟邻近组织环境中造血发育过程的研究方法具有重要意义。他们建立的人类多能干细胞衍生的心脏形成类器官(HFO)，再现了心脏、血管系统和前肠共同发育的各个方面。

调节人类多能干细胞衍生的心脏形成类器官(HFO)的分化，该课题组人员在这里报道造血HFO的产生。在维持功能性心室样心脏原的同时，造血HFO包括一个间充质嵌入的造血内皮层，包括多种造血衍生物和具有红髓和淋巴潜能的造血祖细胞，反映了原始和最终造血的各个方面。该模型使心脏、内皮和多能造血组织在形态结构上能够在体内共同发育，相当于胚胎内造血区，促进体外造血研究。

附：英文原文

Title: Blood-generating heart-forming organoids recapitulate co-development of the human haematopoietic system and the embryonic heart

Author: Dardano, Miriana, Kleemi, Felix, Kosanke, Maike, Lang, Dorina, Wilson, Liam, Franke, Annika, Teske, Jana, Shivaraj, Akshatha, de la Roche, Jeanne, Fischer, Martin, Lange, Lucas, Schambach, Axel, Drakhlis, Lika, Zweigerdt, Robert

Issue&Volume: 2024-10-08

Abstract: Despite the biomedical importance of haematopoietic stem cells and haematopoietic progenitor cells, their in vitro stabilization in a developmental context has not been achieved due to limited knowledge of signals and markers specifying the multiple haematopoietic waves as well as ethically restricted access to the human embryo. Thus, an in vitro approach resembling aspects of haematopoietic development in the context of neighbouring tissues is of interest. Our established human pluripotent stem cell-derived heart-forming organoids (HFOs) recapitulate aspects of heart, vasculature and foregut co-development. Modulating HFO differentiation, we here report the generation of blood-generating HFOs. While maintaining a functional ventricular-like heart anlagen, blood-generating HFOs comprise a mesenchyme-embedded haemogenic endothelial layer encompassing multiple haematopoietic derivatives and haematopoietic progenitor cells with erythro-myeloid and lymphoid potential, reflecting aspects of primitive and definitive haematopoiesis. The model enables the morphologically structured co-development of cardiac, endothelial and multipotent haematopoietic tissues equivalent to the intra-embryonic haematopoietic region in vivo, promoting research on haematopoiesis in vitro.

DOI: 10.1038/s41556-024-01526-4

Source: https://www.nature.com/articles/s41556-024-01526-4