A parallelized, perfused 3D triculture model of leukemia for in vitro drug testing of chemotherapeutics. (1st July 2022)

• Record Type: Journal Article
• Authors: Zippel, Sabrina; Dilger, Nadine; Chatterjee, Chandralekha; Raic, Annamarija; Brenner-Weiß, Gerald; Schadzek, Patrik; Rapp, Bastian E; Lee-Thedieck, Cornelia
• Is Part Of: Biofabrication. Volume 14:Number 3(2022)
• Publication Date: 2022-07-01
• Subjects: magnetic hydrogels -- leukemic niche -- hematopoietic stem and progenitor cells -- chemotherapeutics -- drug testing; Biomedical engineering -- Periodicals; Tissue engineering -- Periodicals; Biomedical materials -- Microstructure -- Periodicals; Bioengineering -- Periodicals; 610.28
• DOI: 10.1088/1758-5090/ac6a7e
• Languages: English
• ISSNs: 1758-5082

Abstract

Abstract: Leukemia patients undergo chemotherapy to combat the leukemic cells (LCs) in the bone marrow. During therapy not only the LCs, but also the blood-producing hematopoietic stem and progenitor cells (HSPCs) may be destroyed. Chemotherapeutics targeting only the LCs are urgently needed to overcome this problem and minimize life-threatening side-effects. Predictive in vitro drug testing systems allowing simultaneous comparison of various experimental settings would enhance the efficiency of drug development. Here, we present a three-dimensional (3D) human leukemic bone marrow model perfused using a magnetic, parallelized culture system to ensure media exchange. Chemotherapeutic treatment of the acute myeloid leukemia cell line KG-1a in 3D magnetic hydrogels seeded with mesenchymal stem/stromal cells (MSCs) revealed a greater resistance of KG-1a compared to 2D culture. In 3D tricultures with HSPCs, MSCs and KG-1a, imitating leukemic bone marrow, HSPC proliferation decreased while KG-1a cells remained unaffected post treatment. Non-invasive metabolic profiling enabled continuous monitoring of the system. Our results highlight the importance of using biomimetic 3D platforms with proper media exchange and co-cultures for creating in vivo -like conditions to enable in vitro drug testing. This system is a step towards drug testing in biomimetic, parallelized in vitro approaches, facilitating the discovery of new anti-leukemic drugs.