1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA. [2].
1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA. [2] Boston University School of Medicine, Boston, Massachusetts, USA. [3].
Nat Methods. 2014 Jun;11(6):663-9. doi: 10.1038/nmeth.2938. Epub 2014 May 4.
Current in vitro hematopoiesis models fail to demonstrate the cellular diversity and complex functions of living bone marrow; hence, most translational studies relevant to the hematologic system are conducted in live animals. Here we describe a method for fabricating 'bone marrow-on-a-chip' that permits culture of living marrow with a functional hematopoietic niche in vitro by first engineering new bone in vivo, removing it whole and perfusing it with culture medium in a microfluidic device. The engineered bone marrow (eBM) retains hematopoietic stem and progenitor cells in normal in vivo-like proportions for at least 1 week in culture. eBM models organ-level marrow toxicity responses and protective effects of radiation countermeasure drugs, whereas conventional bone marrow culture methods do not. This biomimetic microdevice offers a new approach for analysis of drug responses and toxicities in bone marrow as well as for study of hematopoiesis and hematologic diseases in vitro.
目前的体外造血模型未能展示活骨髓的细胞多样性和复杂功能；因此，大多数与血液系统相关的转化研究都是在活体动物中进行的。在这里，我们描述了一种制造“芯片上骨髓”的方法，该方法通过首先在体内工程新骨，将其完整取出并在微流控装置中用培养基灌注，从而允许体外培养具有功能性造血龛的活骨髓。工程化骨髓（eBM）在培养中至少 1 周内保持与体内正常比例的造血干/祖细胞。eBM 模型器官水平的骨髓毒性反应和辐射对策药物的保护作用，而传统的骨髓培养方法则不能。这种仿生微器件为分析骨髓中的药物反应和毒性以及体外研究造血和血液疾病提供了一种新方法。
