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Frenz-Wiessner, S.* ; Fairley, S.D.* ; Buser, M. ; Goek, I.* ; Salewskij, K.* ; Jonsson, G.* ; Illig, D.* ; Zu Putlitz, B.* ; Petersheim, D.* ; Li, Y.* ; Chen, P.H.* ; Kalauz, M.* ; Conca, R.* ; Sterr, M. ; Geuder, J.* ; Mizoguchi, Y.* ; Megens, R.T.A.* ; Linder, M.I.* ; Kotlarz, D.* ; Rudelius, M.* ; Penninger, J.M.* ; Marr, C. ; Klein, C.*

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

Nat. Methods, DOI: 10.1038/s41592-024-02172-2 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Human Hematopoietic Stem; Haemogenic Endothelium; Single-cell; T-cells; Progenitors; Blood; Mouse; Differentiation; Identification; Trafficking
ISSN (print) / ISBN 1548-7091
e-ISSN 1548-7105
Journal Nature Methods
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of AI for Health (AIH)
Institute of Diabetes and Regeneration Research (IDR)
Grants VEO-IBD-Consortium
Leona M. and Harry B. Helmsley Charitable Trust
Hector Foundation
Else Kroener-Fresenius-Stiftung
German Center for Infection Research (DZIF)
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Reinhard Frank-Stiftung
City of Vienna
National Institute of Health
German Federal Ministry of Education and Research (BMBF)
Dr. von Hauner Children's Hospital

EFPIA (European Federation of Pharmaceutical Industries and Associations)
European Union
Innovative Medicines Initiative 2 Joint Undertaking
Diamond-Blackfan-Anemia Fundraising
Leducq Foundation
Allen Distinguished Investigator program
Canada 150 Research Chairs Program
T. von Zastrow foundation
Fundacio La Marato de TV3
Medical University of Vienna
Austrian Academy of Sciences
Hightech Agenda Bayern
European Research Council (ERC) und the European Union
Austrian Federal Ministry of Education, Science and Research