title: Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro.
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.
authors.affiliation: 1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA. [2].
authors.forename: Yu-suke
authors.initials: YS
authors.lastname: Torisawa
authors.affiliation: 1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA. [2] Boston University School of Medicine, Boston, Massachusetts, USA. [3].
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Spina
authors.affiliation: Vascular Biology Program, Departments of Pathology and Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Tadanori
authors.initials: T
authors.lastname: Mammoto
authors.affiliation: Vascular Biology Program, Departments of Pathology and Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Mammoto
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Weaver
authors.affiliation: Vascular Biology Program, Departments of Pathology and Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Tat
authors.affiliation: 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.
authors.forename: James J
authors.initials: JJ
authors.lastname: Collins
authors.affiliation: 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.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Ingber
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000737:chemistry / Q000502:physiology*; D018929:Cell Culture Techniques; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice; D046210:Microfluidic Analytical Techniques