Modeling Hematopoiesis and Responses to Radiation Countermeasures in a Bone Marrow-on-a-Chip

Tissue Eng Part C Methods. 2016 May;22(5):509-15. doi: 10.1089/ten.TEC.2015.0507. Epub 2016 Apr 20.


Studies on hematopoiesis currently rely on animal models because in vitro culture methods do not accurately recapitulate complex bone marrow physiology. We recently described a bone marrow-on-a-chip microfluidic device that enables the culture of living hematopoietic bone marrow and mimics radiation toxicity in vitro. In the present study, we used this microdevice to demonstrate continuous blood cell production in vitro and model bone marrow responses to potential radiation countermeasure drugs. The device maintained mouse hematopoietic stem and progenitor cells in normal proportions for at least 2 weeks in culture. Increases in the number of leukocytes and red blood cells into the microfluidic circulation also could be detected over time, and addition of erythropoietin induced a significant increase in erythrocyte production. Exposure of the bone marrow chip to gamma radiation resulted in reduction of leukocyte production, and treatment of the chips with two potential therapeutics, granulocyte-colony stimulating factor or bactericidal/permeability-increasing protein (BPI), induced significant increases in the number of hematopoietic stem cells and myeloid cells in the fluidic outflow. In contrast, BPI was not found to have any effect when analyzed using static marrow cultures, even though it has been previously shown to accelerate recovery from radiation-induced toxicity in vivo. These findings demonstrate the potential value of the bone marrow-on-a-chip for modeling blood cell production, monitoring responses to hematopoiesis-modulating drugs, and testing radiation countermeasures in vitro.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / administration & dosage
  • Blood Proteins / administration & dosage
  • Bone Marrow / pathology*
  • Bone Marrow / radiation effects
  • Gamma Rays / adverse effects*
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Hematopoiesis / physiology*
  • Hematopoiesis / radiation effects
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Microfluidic Analytical Techniques / instrumentation*
  • Models, Biological*
  • Myeloid Cells / cytology*
  • Myeloid Cells / radiation effects


  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • bactericidal permeability increasing protein
  • Granulocyte Colony-Stimulating Factor