02118nas a2200445   4500000000100000000000100001008004100002260001200043653001600055653002200071653001900093653001800112653002500130653001800155653002900173653001100202653002600213653002000239653002000259653002300279100001900302700002200321700002100343700002300364700002600387700001800413700002000431700002400451700001800475700002000493700001800513700002600531700001900557700002100576245006700597300001100664490000800675520097500683022001401658       2022                            d  c2022-0110abone marrow10aBone Marrow Cells10aBone and Bones10aBreast cancer10aCell Differentiation10aHematopoiesis10aHematopoietic Stem Cells10aHumans10aLab-On-A-Chip Devices10aorgan-on-a-chip10aStem Cell Niche10aTissue engineering1 aDrew E. Glaser1 aMatthew B. Curtis1 aPeter A. Sariano1 aZachary A. Rollins1 aBhupinder S. Shergill1 aAravind Anand1 aAlyssa M. Deely1 aVenktesh S. Shirure1 aLeif Anderson1 aJeremy M. Lowen1 aNatalie R. Ng1 aKatherine Weilbaecher1 aDaniel C. Link1 aSteven C. George00aOrgan-on-a-chip model of vascularized human bone marrow niches  a1212450 v2803 aBone 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.  a1878-5905