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Credit: James Weaver,
Harvard’s Wyss Institute
Researchers have created a device that reproduces the structure, function, and cellular make-up of bone marrow, according to a paper published
in Nature Methods.
The device, dubbed “bone marrow on a chip,” could serve as a new tool for testing the effects of radiation and other toxic agents on whole bone marrow.
The researchers believe this bone marrow on a chip could provide an alternative to animal testing, although the device itself was generated in mice.
The team also thinks that, in the future, the engineered bone marrow could be used to maintain a cancer patient’s own marrow temporarily during radiation or high-dose chemotherapy.
In an initial test, the engineered bone marrow withered in response to radiation, just as natural bone marrow does. And, as in natural marrow, granulocyte colony-stimulating factor conferred a protective effect on the engineered marrow.
“Bone marrow is an incredibly complex organ that is responsible for producing all of the blood cell types in our body, and our bone marrow chips are able to recapitulate this complexity in its entirety and maintain it in a functional form in vitro,” said study author Donald Ingber, MD, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston.
Dr Ingber leads an effort to develop human organs on chips—small microfluidic devices that mimic the physiology of living organs. To build these devices, researchers combine multiple types of cells from an organ on a plastic microfluidic device, while steadily supplying nutrients, removing waste, and applying mechanical forces the tissues would face in the body.
But bone marrow is so complex that Dr Ingber and his colleagues needed a new approach to mimic organ function. Rather than trying to reproduce such a complex structure cell by cell, the team used mice.
Specifically, the researchers packed dried bone powder into an open, ring-shaped mold the size of a coin battery and implanted the mold under the skin on the animal’s back.
After 8 weeks, the team surgically removed the disk-shaped bone that had formed in the mold and examined it with a specialized CAT scanner. The scan showed a honeycomb-like structure that looked identical to natural trabecular bone.
The marrow looked like the real thing as well. When the researchers stained the tissue and examined it under a microscope, the marrow was packed with blood cells, just like marrow from a living mouse.
And when the team sorted the bone marrow cells by type and tallied their numbers, the mix of different types of blood and immune cells in the engineered bone marrow was identical to that in a mouse thighbone.
To sustain the engineered bone marrow outside of a living animal, the researchers surgically removed the engineered bone from mice, then placed it in a microfluidic device that mimics the circulation the tissue would experience in the body.
Marrow in the device remained healthy for up to 1 week. This is typically long enough to test the toxicity and effectiveness of a new drug, the team said.
The device also passed an initial test of its drug-testing capabilities. Like marrow from live mice, this engineered marrow was susceptible to radiation, but granulocyte colony-stimulating factor conferred a protective effect.
The researchers believe that, in the future, they could potentially grow human bone marrow in immune-deficient mice. And their bone marrow on a chip could generate blood cells, which could circulate in an artificial circulatory system to supply a network of other organs on chips. 
Credit: James Weaver,
Harvard’s Wyss Institute
Researchers have created a device that reproduces the structure, function, and cellular make-up of bone marrow, according to a paper published
in Nature Methods.
The device, dubbed “bone marrow on a chip,” could serve as a new tool for testing the effects of radiation and other toxic agents on whole bone marrow.
The researchers believe this bone marrow on a chip could provide an alternative to animal testing, although the device itself was generated in mice.
The team also thinks that, in the future, the engineered bone marrow could be used to maintain a cancer patient’s own marrow temporarily during radiation or high-dose chemotherapy.
In an initial test, the engineered bone marrow withered in response to radiation, just as natural bone marrow does. And, as in natural marrow, granulocyte colony-stimulating factor conferred a protective effect on the engineered marrow.
“Bone marrow is an incredibly complex organ that is responsible for producing all of the blood cell types in our body, and our bone marrow chips are able to recapitulate this complexity in its entirety and maintain it in a functional form in vitro,” said study author Donald Ingber, MD, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston.
Dr Ingber leads an effort to develop human organs on chips—small microfluidic devices that mimic the physiology of living organs. To build these devices, researchers combine multiple types of cells from an organ on a plastic microfluidic device, while steadily supplying nutrients, removing waste, and applying mechanical forces the tissues would face in the body.
But bone marrow is so complex that Dr Ingber and his colleagues needed a new approach to mimic organ function. Rather than trying to reproduce such a complex structure cell by cell, the team used mice.
Specifically, the researchers packed dried bone powder into an open, ring-shaped mold the size of a coin battery and implanted the mold under the skin on the animal’s back.
After 8 weeks, the team surgically removed the disk-shaped bone that had formed in the mold and examined it with a specialized CAT scanner. The scan showed a honeycomb-like structure that looked identical to natural trabecular bone.
The marrow looked like the real thing as well. When the researchers stained the tissue and examined it under a microscope, the marrow was packed with blood cells, just like marrow from a living mouse.
And when the team sorted the bone marrow cells by type and tallied their numbers, the mix of different types of blood and immune cells in the engineered bone marrow was identical to that in a mouse thighbone.
To sustain the engineered bone marrow outside of a living animal, the researchers surgically removed the engineered bone from mice, then placed it in a microfluidic device that mimics the circulation the tissue would experience in the body.
Marrow in the device remained healthy for up to 1 week. This is typically long enough to test the toxicity and effectiveness of a new drug, the team said.
The device also passed an initial test of its drug-testing capabilities. Like marrow from live mice, this engineered marrow was susceptible to radiation, but granulocyte colony-stimulating factor conferred a protective effect.
The researchers believe that, in the future, they could potentially grow human bone marrow in immune-deficient mice. And their bone marrow on a chip could generate blood cells, which could circulate in an artificial circulatory system to supply a network of other organs on chips.
Credit: James Weaver,
Harvard’s Wyss Institute
Researchers have created a device that reproduces the structure, function, and cellular make-up of bone marrow, according to a paper published
in Nature Methods.
The device, dubbed “bone marrow on a chip,” could serve as a new tool for testing the effects of radiation and other toxic agents on whole bone marrow.
The researchers believe this bone marrow on a chip could provide an alternative to animal testing, although the device itself was generated in mice.
The team also thinks that, in the future, the engineered bone marrow could be used to maintain a cancer patient’s own marrow temporarily during radiation or high-dose chemotherapy.
In an initial test, the engineered bone marrow withered in response to radiation, just as natural bone marrow does. And, as in natural marrow, granulocyte colony-stimulating factor conferred a protective effect on the engineered marrow.
“Bone marrow is an incredibly complex organ that is responsible for producing all of the blood cell types in our body, and our bone marrow chips are able to recapitulate this complexity in its entirety and maintain it in a functional form in vitro,” said study author Donald Ingber, MD, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston.
Dr Ingber leads an effort to develop human organs on chips—small microfluidic devices that mimic the physiology of living organs. To build these devices, researchers combine multiple types of cells from an organ on a plastic microfluidic device, while steadily supplying nutrients, removing waste, and applying mechanical forces the tissues would face in the body.
But bone marrow is so complex that Dr Ingber and his colleagues needed a new approach to mimic organ function. Rather than trying to reproduce such a complex structure cell by cell, the team used mice.
Specifically, the researchers packed dried bone powder into an open, ring-shaped mold the size of a coin battery and implanted the mold under the skin on the animal’s back.
After 8 weeks, the team surgically removed the disk-shaped bone that had formed in the mold and examined it with a specialized CAT scanner. The scan showed a honeycomb-like structure that looked identical to natural trabecular bone.
The marrow looked like the real thing as well. When the researchers stained the tissue and examined it under a microscope, the marrow was packed with blood cells, just like marrow from a living mouse.
And when the team sorted the bone marrow cells by type and tallied their numbers, the mix of different types of blood and immune cells in the engineered bone marrow was identical to that in a mouse thighbone.
To sustain the engineered bone marrow outside of a living animal, the researchers surgically removed the engineered bone from mice, then placed it in a microfluidic device that mimics the circulation the tissue would experience in the body.
Marrow in the device remained healthy for up to 1 week. This is typically long enough to test the toxicity and effectiveness of a new drug, the team said.
The device also passed an initial test of its drug-testing capabilities. Like marrow from live mice, this engineered marrow was susceptible to radiation, but granulocyte colony-stimulating factor conferred a protective effect.
The researchers believe that, in the future, they could potentially grow human bone marrow in immune-deficient mice. And their bone marrow on a chip could generate blood cells, which could circulate in an artificial circulatory system to supply a network of other organs on chips.