Organ-on-a-chip model of vascularized human bone marrow niches

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...

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Vydáno v:Biomaterials Ročník 280; s. 121245
Hlavní autoři: Glaser, Drew E., Curtis, Matthew B., Sariano, Peter A., Rollins, Zachary A., Shergill, Bhupinder S., Anand, Aravind, Deely, Alyssa M., Shirure, Venktesh S., Anderson, Leif, Lowen, Jeremy M., Ng, Natalie R., Weilbaecher, Katherine, Link, Daniel C., George, Steven C.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Netherlands Elsevier Ltd 01.01.2022
Témata:
biocompatible materials
Bone and Bones
Bone Marrow
Bone Marrow Cells
Breast cancer
Cell Differentiation - physiology
dormancy
doxorubicin
Hematopoiesis
Hematopoiesis - physiology
Hematopoietic Stem Cells
Humans
Lab-On-A-Chip Devices
neoplasm cells
neutrophils
Organ-on-a-chip
Stem Cell Niche
stem cells
Tissue engineering
Organ-on-a-chip
Breast cancer
Tissue engineering
Hematopoiesis
ISSN:0142-9612, 1878-5905, 1878-5905
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Shrnutí: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. •An organ-on-a-chip recreates the bone marrow's endosteal and perivascular niches.•The tissue engineered model is vascularized and maintains hematopoietic stem cells.•The microfluidic device supports hematopoiesis and mimics the in vivo drug response.•The organ-on-a-chip permits egress of leukocytes to mimic peripheral circulation.•Interactions between cancer and bone marrow can be studied using the technology.
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ISSN:0142-9612
1878-5905
1878-5905
DOI:10.1016/j.biomaterials.2021.121245