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

Drew E. Glaser, Matthew B. Curtis, Peter A. Sariano, Zachary A. Rollins, Bhupinder S. Shergill, Aravind Anand, Alyssa M. Deely, Venktesh S. Shirure, Leif Anderson, Jeremy M. Lowen, Natalie R. Ng, Katherine Weilbaecher, Daniel C. Link, Steven C. George

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Article number121245
JournalBiomaterials
Volume280
DOIs
StatePublished - Jan 2022

Keywords

  • Breast cancer
  • Hematopoiesis
  • Organ-on-a-chip
  • Tissue engineering

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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