Self-organization of the hematopoietic vascular niche and emergent innate immunity on a chip

Here, we present a bioengineering approach to emulate the human bone marrow in vitro. Our developmentally inspired method uses self-organization of human hematopoietic stem and progenitor cells and vascular endothelial cells cultured in a three-dimensional microphysiological system to create vascularized, perfusable tissue constructs that resemble the hematopoietic vascular niche of the human marrow. The microengineered niche is capable of multilineage hematopoiesis and can generate functionally mature human myeloid cells that can intravasate into perfused blood vessels, providing a means to model the mobilization of innate immune cells from the marrow. We demonstrate the application of this system by presenting a specialized model of ionizing radiation-induced bone marrow injury and a multiorgan model of acute innate immune responses to bacterial lung infection. Furthermore, we introduce an advanced platform that enables large-scale integration and automated experimentation of the engineered hematopoietic tissues for preclinical screening of myelotoxicity due to anti-cancer drugs. [Display omitted] •Microengineered model of the hematopoietic vascular niche of the human bone marrow•In vitro modeling of ionizing radiation-induced acute bone marrow injury•Microphysiological model of innate immune response to bacterial lung infection•Automated screening platform to assess myelotoxicity of anticancer drugs Georgescu et al. present a bioengineered platform to mimic the specialized microenvironment of the human bone marrow responsible for producing blood cells. They demonstrate how this microphysiological system can be used to emulate and predict responses of the hematopoietic niche to ionizing radiation, bacterial lung infection, or anticancer drugs.