TY - JOUR
KW - bone marrow
KW - Bone Marrow Cells
KW - Bone and Bones
KW - Breast cancer
KW - Cell Differentiation
KW - Hematopoiesis
KW - Hematopoietic Stem Cells
KW - Humans
KW - Lab-On-A-Chip Devices
KW - organ-on-a-chip
KW - Stem Cell Niche
KW - Tissue engineering
AU - Drew E. Glaser
AU - Matthew B. Curtis
AU - Peter A. Sariano
AU - Zachary A. Rollins
AU - Bhupinder S. Shergill
AU - Aravind Anand
AU - Alyssa M. Deely
AU - Venktesh S. Shirure
AU - Leif Anderson
AU - Jeremy M. Lowen
AU - Natalie R. Ng
AU - Katherine Weilbaecher
AU - Daniel C. Link
AU - Steven C. George
AB - 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.
BT - Biomaterials
DA - 2022-01
DO - 10.1016/j.biomaterials.2021.121245
LA - eng
N2 - 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.
PY - 2022
EP - 121245
T2 - Biomaterials
TI - Organ-on-a-chip model of vascularized human bone marrow niches
VL - 280
SN - 1878-5905
ER -