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Supp Table 4 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies

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posted on 2023-04-04, 00:20 authored by Abdullah O. Khan, Antonio Rodriguez-Romera, Jasmeet S. Reyat, Aude-Anais Olijnik, Michela Colombo, Guanlin Wang, Wei Xiong Wen, Nikolaos Sousos, Lauren C. Murphy, Beata Grygielska, Gina Perrella, Christopher B. Mahony, Rebecca E. Ling, Natalina E. Elliott, Christina Simoglou Karali, Andrew P. Stone, Samuel Kemble, Emily A. Cutler, Adele K. Fielding, Adam P. Croft, David Bassett, Gowsihan Poologasundarampillai, Anindita Roy, Sarah Gooding, Julie Rayes, Kellie R. Machlus, Bethan Psaila

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Funding

Cancer Research UK (CRUK)

National Heart, Lung, and Blood Institute (NHLBI)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

United States Department of Health and Human Services

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Engineering and Physical Sciences Research Council (EPSRC)

Wellcome Trust (WT)

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ARTICLE ABSTRACT

A lack of models that recapitulate the complexity of human bone marrow has hampered mechanistic studies of normal and malignant hematopoiesis and the validation of novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from induced pluripotent stem cells committed to mesenchymal, endothelial, and hematopoietic lineages. These 3D structures capture key features of human bone marrow—stroma, lumen-forming sinusoids, and myeloid cells including proplatelet-forming megakaryocytes. The organoids supported the engraftment and survival of cells from patients with blood malignancies, including cancer types notoriously difficult to maintain ex vivo. Fibrosis of the organoid occurred following TGFβ stimulation and engraftment with myelofibrosis but not healthy donor–derived cells, validating this platform as a powerful tool for studies of malignant cells and their interactions within a human bone marrow–like milieu. This enabling technology is likely to accelerate the discovery and prioritization of novel targets for bone marrow disorders and blood cancers. We present a human bone marrow organoid that supports the growth of primary cells from patients with myeloid and lymphoid blood cancers. This model allows for mechanistic studies of blood cancers in the context of their microenvironment and provides a much-needed ex vivo tool for the prioritization of new therapeutics.See related commentary by Derecka and Crispino, p. 263.This article is highlighted in the In This Issue feature, p. 247

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    Cancer Discovery

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    cancer

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    CC BY

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