Karlsruhe Institute of Technology (KIT), Institute of Functional Interfaces, Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany.
Institute for Tissue Engineering and Regenerative Medicine, University of Würzburg, 97070, Würzburg, Germany.
Sci Rep. 2017 Jul 4;7(1):4625. doi: 10.1038/s41598-017-04808-0.
Hematopoietic stem cells (HSCs) in the bone marrow are able to differentiate into all types of blood cells and supply the organism each day with billions of fresh cells. They are applied to cure hematological diseases such as leukemia. The clinical need for HSCs is high and there is a demand for being able to control and multiply HSCs in vitro. The hematopoietic system is highly proliferative and thus sensitive to anti-proliferative drugs such as chemotherapeutics. For many of these drugs suppression of the hematopoietic system is the dose-limiting toxicity. Therefore, biomimetic 3D models of the HSC niche that allow to control HSC behavior in vitro and to test drugs in a human setting are relevant for the clinics and pharmacology. Here, we describe a perfused 3D bone marrow analog that allows mimicking the HSC niche under steady-state and activated conditions that favor either HSC maintenance or differentiation, respectively, and allows for drug testing.
骨髓中的造血干细胞(HSCs)能够分化为所有类型的血细胞,并每天为机体提供数十亿个新细胞。它们被用于治疗白血病等血液疾病。临床对 HSCs 的需求很高,因此需要能够在体外控制和扩增 HSCs。造血系统具有高度的增殖能力,因此对化疗等抗增殖药物敏感。对于许多这些药物来说,抑制造血系统是剂量限制毒性。因此,模拟 HSC 龛位的仿生 3D 模型能够在体外控制 HSC 行为,并在人体环境中测试药物,这对于临床和药理学都具有重要意义。在这里,我们描述了一种灌注的 3D 骨髓模拟物,它可以模拟稳态和激活条件下的 HSC 龛位,分别有利于 HSC 的维持或分化,并允许进行药物测试。