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Organ-on-a-chip model of vascularized human bone marrow niches
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Abstract
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.
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“BMoaC supported proliferation and differentiation of hematopoietic stem/progenitor cells (HSPCs) into monocytes and neutrophils.”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [118]
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Metadata
- Authors
- Glaser, D. E., Curtis, M. B., Sariano, P. A., Rollins, Z. A., Shergill, B. S., Anand, A., Deely, A. M., Shirure, V. S., Anderson, L., Lowen, J. M., Ng, N. R., Weilbaecher, K., Link, D. C., & George, S. C.
- Affiliations
- University of California, Davis (US)
- Washington University in St. Louis (US)
- Corresponding author
- George, Steven C.
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2022-01
- Volume
- 280
- Pages
- 121245
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC10658812
- OpenAlex
- W3213963490
- Cited by
- 146
- References
- 65
- Citations by year
- 2026: 34 · 2025: 36 · 2024: 35 · 2023: 20 · 2022: 15
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Biomaterials (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (F32CA210540-01A1, R21CA208519, UH3TR000481)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- bone marrow microenvironment, organ-on-a-chip, perivascular niche, endosteal niche, hematopoietic stem and progenitor cells, CD34+ cells, granulocyte colony-stimulating factor, 3D in vitro model, drug response
- MeSH terms
- Bone and Bones, Bone Marrow, Bone Marrow Cells, Cell Differentiation, Hematopoiesis, Hematopoietic Stem Cells, Humans, Stem Cell Niche, Lab-On-A-Chip Devices
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