High-throughput formulation of reproducible 3D cancer microenvironments for drug testing in myeloid leukemia.

IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL Biofabrication Pub Date : 2024-12-16 DOI:10.1088/1758-5090/ad998d
M Rudzinska-Radecka, L Turos-Korgul, D Mukherjee, P Podszywalow-Bartnicka, K Piwocka, J Guzowski
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引用次数: 0

Abstract

Leukemic microenvironment has been recognized as a factor that strongly supports the mechanisms of resistance. Therefore, targeting the microenvironment is currently one of the major directions in drug development and preclinical studies in leukemia. Despite the variety of available leukemia 3D culture models, the reproducible generation of miniaturized leukemic microenvironments, suitable for high-throughput drug testing, has remained a challenge. Here, we use droplet microfluidics to generate tens of thousands of highly monodisperse leukemic-bone marrow microenvironments within minutes. We employ gelatin methacryloyl (GelMA) as a model extracellular matrix (ECM) and tune the concentration of the biopolymer, check the impact of other components of the ECM (hyaluronic acid), cell concentration and the ratio of leukemic cells to bone marrow cells within the microbeads to establish the optimal conditions for microtissue formation. We administer model kinase inhibitor, imatinib, at various concentrations to the encapsulated leukemic microtissues, and, via comparing mono- and co-culture conditions (cancer alone vs cancer-stroma), we find that the stroma-leukemia crosstalk systematically protects the encapsulated cells against the drug-induced cytotoxicity. With that we demonstrate that our system mimics the physiological stroma-dependent protection. We discuss applicability of our model to (i) studying the role of direct- or close-contact interactions between the leukemia and bone marrow cells embedded in microscale 3D ECM on the stroma-mediated protection, and (ii) high-throughput screening of anti-cancer therapeutics in personalized leukemia therapies.

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来源期刊
Biofabrication
Biofabrication ENGINEERING, BIOMEDICAL-MATERIALS SCIENCE, BIOMATERIALS
CiteScore
17.40
自引率
3.30%
发文量
118
审稿时长
2 months
期刊介绍: Biofabrication is dedicated to advancing cutting-edge research on the utilization of cells, proteins, biological materials, and biomaterials as fundamental components for the construction of biological systems and/or therapeutic products. Additionally, it proudly serves as the official journal of the International Society for Biofabrication (ISBF).
期刊最新文献
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