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Nat Methods. 2014 Jun;11(6):663-9. doi: 10.1038/nmeth.2938. Epub 2014 May 4.

Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro.

Author information

1
1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA. [2].
2
1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA. [2] Boston University School of Medicine, Boston, Massachusetts, USA. [3].
3
Vascular Biology Program, Departments of Pathology and Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, USA.
4
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
5
1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA. [2] Boston University School of Medicine, Boston, Massachusetts, USA. [3] Howard Hughes Medical Institute, Boston University, Boston, Massachusetts, USA. [4] Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
6
1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA. [2] Vascular Biology Program, Departments of Pathology and Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, USA. [3] School of Engineering and Applied Science, Harvard University, Cambridge, Massachusetts, USA.

Abstract

Current in vitro hematopoiesis models fail to demonstrate the cellular diversity and complex functions of living bone marrow; hence, most translational studies relevant to the hematologic system are conducted in live animals. Here we describe a method for fabricating 'bone marrow-on-a-chip' that permits culture of living marrow with a functional hematopoietic niche in vitro by first engineering new bone in vivo, removing it whole and perfusing it with culture medium in a microfluidic device. The engineered bone marrow (eBM) retains hematopoietic stem and progenitor cells in normal in vivo-like proportions for at least 1 week in culture. eBM models organ-level marrow toxicity responses and protective effects of radiation countermeasure drugs, whereas conventional bone marrow culture methods do not. This biomimetic microdevice offers a new approach for analysis of drug responses and toxicities in bone marrow as well as for study of hematopoiesis and hematologic diseases in vitro.

PMID:
24793454
DOI:
10.1038/nmeth.2938
[Indexed for MEDLINE]
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