Department of Biomedical Engineering, University of California, Davis, 451 E Health Sciences Dr, GBSF 2303, Davis, CA 95616, USA.
Department of Chemical Engineering, University of California, Davis, 1 Shields Ave, Bainer 3106, Davis, CA 95616, USA.
Biomaterials. 2022 Jan;280:121245. doi: 10.1016/j.biomaterials.2021.121245. Epub 2021 Nov 12.
Bone marrow niches (endosteal and perivascular) play important roles in both normal bone marrow function and pathological processes such as cancer cell dormancy. Unraveling the mechanisms underlying these events in humans has been severely limited by models that cannot dissect dynamic events at the niche level. Utilizing microfluidic and stem cell technologies, we present a 3D in vitro model of human bone marrow that contains both the perivascular and endosteal niches, complete with dynamic, perfusable vascular networks. We demonstrate that our model can replicate in vivo bone marrow function, including maintenance and differentiation of CD34 hematopoietic stem/progenitor cells, egress of neutrophils (CD66b), and niche-specific responses to doxorubicin and granulocyte-colony stimulating factor. Our platform provides opportunities to accelerate current understanding of human bone marrow function and drug response with high spatial and temporal resolution.
骨髓龛（骨内膜和血管周）在正常骨髓功能和癌症细胞休眠等病理过程中发挥重要作用。由于模型无法剖析龛位水平的动态事件，因此严重限制了对这些事件在人类中的机制的研究。我们利用微流控和干细胞技术，提供了一个包含血管周和骨内膜龛的人类骨髓的 3D 体外模型，其中包含动态可灌注的血管网络。我们证明，我们的模型可以复制体内骨髓功能，包括 CD34 造血干/祖细胞的维持和分化、中性粒细胞（CD66b）的迁出，以及对阿霉素和粒细胞集落刺激因子的龛位特异性反应。我们的平台为加速对人类骨髓功能和药物反应的理解提供了机会，具有高时空分辨率。
