德国慕尼黑-路德维希-马克西米利安大学附属医院Christoph Klein研究团队取得一项新突破。他们利用人诱导多能干细胞（iPSCs）生成了复杂的骨髓（BM）器官组织。相关论文发表在2024年2月19日出版的《自然-方法学》杂志上。

研究人员建立了一种利用人诱导多能干细胞生成复杂骨髓样器官组织（BMOs）的方法。BMOs具有关键的细胞类型，它们能自我组装成空间定义的三维结构，具有与造血微环境相似的细胞、结构和分子特征。BMOs具有类似活体的血管网络、多能间充质干细胞/祖细胞、支持中性粒细胞分化以及对炎症刺激反应等功能特性。

单细胞RNA测序揭示了差异细胞组成，包括表达胎儿造血干细胞基因的造血干细胞/祖细胞（HSPC）群。BMO衍生的HSPCs还具有淋巴潜能，其中一个亚群在小鼠异种移植后表现出短暂的移植潜能。该研究表明，BMOs可用于造血发育和先天性造血错误建模，正如人类VPS45缺乏症所示。因此，iPSC衍生的BMOs可作为人类BM微环境生理相关的体外模型，用于研究造血发育和BM疾病。

附：英文原文

Title: Generation of complex bone marrow organoids from human induced pluripotent stem cells

Author: Frenz-Wiessner, Stephanie, Fairley, Savannah D., Buser, Maximilian, Goek, Isabel, Salewskij, Kirill, Jonsson, Gustav, Illig, David, zu Putlitz, Benedicta, Petersheim, Daniel, Li, Yue, Chen, Pin-Hsuan, Kalauz, Martina, Conca, Raffaele, Sterr, Michael, Geuder, Johanna, Mizoguchi, Yoko, Megens, Remco T. A., Linder, Monika I., Kotlarz, Daniel, Rudelius, Martina, Penninger, Josef M., Marr, Carsten, Klein, Christoph

Issue&Volume: 2024-02-19

Abstract: The human bone marrow (BM) niche sustains hematopoiesis throughout life. We present a method for generating complex BM-like organoids (BMOs) from human induced pluripotent stem cells (iPSCs). BMOs consist of key cell types that self-organize into spatially defined three-dimensional structures mimicking cellular, structural and molecular characteristics of the hematopoietic microenvironment. Functional properties of BMOs include the presence of an in vivo-like vascular network, the presence of multipotent mesenchymal stem/progenitor cells, the support of neutrophil differentiation and responsiveness to inflammatory stimuli. Single-cell RNA sequencing revealed a heterocellular composition including the presence of a hematopoietic stem/progenitor (HSPC) cluster expressing genes of fetal HSCs. BMO-derived HSPCs also exhibited lymphoid potential and a subset demonstrated transient engraftment potential upon xenotransplantation in mice. We show that the BMOs could enable the modeling of hematopoietic developmental aspects and inborn errors of hematopoiesis, as shown for human VPS45 deficiency. Thus, iPSC-derived BMOs serve as a physiologically relevant in vitro model of the human BM microenvironment to study hematopoietic development and BM diseases.

DOI: 10.1038/s41592-024-02172-2

Source: https://www.nature.com/articles/s41592-024-02172-2