comBO: A combined human bone and lympho-myeloid bone marrow organoid for preclinical modeling of hematopoietic disorders

IF 23.3 1区医学 Q1 CELL & TISSUE ENGINEERING

Cell stem cell Pub Date : 2026-02-23 DOI:10.1016/j.stem.2026.01.010

Yuqi Shen, Camelia Benlabiod, Edmund Watson, Kristian Gurashi, Alex Fower, Antonio Rodriguez-Romera, Jasmeet S. Reyat, Shady Adnan-Awad, Rupen Hargreaves, Samuel Kemble, Charlotte G. Smith, Adam P. Croft, Udo Oppermann, Alia Welsh, Lauren Murphy, Eleanor Murphy, Amirpasha Moetazedian, Natalie Jooss, Zoe C. Wong, Julie Rayes, Abdullah O. Khan

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Abstract

The bone marrow is the primary site of blood and immune cell production in postnatal life. Current human models do not capture lympho-myeloid hematopoiesis and the stromal diversity needed for lifelong blood and immune maintenance. Here, we introduce comBO (combined bone and lympho-myeloid bone marrow organoid), a scalable induced pluripotent stem cell (iPSC)-derived system that generates osteolineage, vascular, lymphoid, and myeloid compartments within a single organoid. Developed under physioxia in granular microgel scaffolds, comBOs improve scalability and reproducibility and sustain long-term lympho-myeloid potential in serial organoid re-seeding assays. Incorporating healthy or malignant donor cells produces “chimeroids” that model physiological and pathological states. Using multiple myeloma as an exemplar, comBOs recapitulate niche remodeling and identify macrophage inhibitory factor (MIF) signaling as a disease driver. MIF inhibition reduces inflammation and myeloma proliferation, highlighting its therapeutic potential. comBOs offer a physiologically faithful bone marrow platform for disease modeling and therapeutic discovery in translational hematology and immunology.

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comBO：用于造血疾病临床前建模的人骨和淋巴骨髓类器官

骨髓是出生后血液和免疫细胞产生的主要部位。目前的人体模型没有捕捉到淋巴-骨髓造血和维持终身血液和免疫所需的基质多样性。在这里，我们介绍了comBO（结合骨和淋巴-髓系骨髓类器官），这是一种可扩展的诱导多能干细胞（iPSC）衍生系统，可在单个类器官内产生骨系、血管、淋巴和髓系隔室。在颗粒微凝胶支架下在生理氧作用下发展，comBOs提高了可扩展性和可重复性，并在一系列类器官重新播种试验中维持长期的淋巴髓细胞潜能。将健康或恶性供体细胞结合产生模拟生理和病理状态的“嵌合体”。以多发性骨髓瘤为例，comBOs总结了生态位重塑，并确定巨噬细胞抑制因子（MIF）信号作为疾病驱动因素。抑制MIF可减少炎症和骨髓瘤增殖，突出其治疗潜力。comBOs为转译血液学和免疫学的疾病建模和治疗发现提供了一个生理上忠实的骨髓平台。

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来源期刊

Cell stem cell 生物-细胞生物学

CiteScore

37.10

自引率

2.50%

发文量

151

审稿时长

42 days

期刊介绍： Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.