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AACR 2025 Poster 5493

3D Bone Marrow Niche: Scalable and Physiologically Relevant Ex Vivo Drug Screening Platform for Hematological Malignancies

Talita Stessuk, Dorrith Verstegen, Sophia Ajala, Hanna Vermeer, Jolie Flach, Marrit Putker, Nataliia Beztsinna and Ludovic Bourre

Preclinical drug screening for hematological cancers like Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM) is hindered by the poor ex vivo viability of primary cells. Traditional 2D and suspension cultures fail to replicate the tumor microenvironment, leading to unreliable predictions of in vivo drug responses.

To address this, we developed a 3D bone marrow niche (BMN) model composed of endothelial-mesenchymal networks embedded in a bioactive hydrogel. This platform supports the survival and proliferation of patient-derived AML and MM cells, enabling medium-throughput drug testing with high-content imaging (HCI) for quantitative analysis.

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  • Physiologically Relevant Model: A 3D BMN system mimics the pre-vascularized bone marrow microenvironment, promoting the survival and outgrowth of primary AML and MM cells.

  • High-Content Imaging-Based Analysis: HCI quantifies drug responses in a clinically relevant setting while also assessing potential off-target effects on stromal components.

  • Enhanced Drug Screening Capabilities: The platform enables medium-throughput testing of standard-of-care therapies, providing valuable insights into patient-specific drug responses.

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