Scientists from Harvard’s Wyss Institute for Biologically Inspired Engineering have described a method for producing a device which closely mimics the composition and architecture of actual bone marrow. This bone marrow-on-a-chip is the first of its kind and adds to the growing repertoire of organs-on-a-chip that this institute has developed. The study has been published in Nature Methods.
This new device could have numerous important applications in medicine. In particular, it is hoped that it may serve as a model to investigate the effects of radiation therapy on bone marrow and in the development of treatments to subvert the damage caused by this type of therapy. Eventually, it could even be used to produce a supply of a patient’s own bone marrow which would be useful in those undergoing harsh cancer treatments.
At the forefront of this pioneering technology is Don Ingber, Founding Director of the Wyss Institute. These organs-on-chips are small microfluidic devices that aim to replicate complex aspects of organs in order to model disease, and possibly to eventually replace the need for animals in drug testing. So far, scientists at the Wyss Institute have developed lung, heart, kidney and gut organs-on-chips, but owing to the intricate nature of bone marrow this particular organ has proved troublesome to accurately model in the past. This has meant that bone marrow studies have previously relied on live animals.
This new device, however, may finally allow scientists to move away from a dependence on in vivo models. “Bone marrow is an incredibly complex organ that is responsible for producing all of the blood cell types of 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 Ingber.
In order to make these devices in the past, scientists combined numerous different cell types from a particular organ on a microfluidic chip and supplied it with nutrients whilst removing waste products. But engineering bone marrow proved trickier and warranted a novel approach. This is because bone marrow is found throughout spongy, honeycomb-like bone called trabecular bone which varies considerably in terms of temperature and oxygen content. Instead of attempting to forge such a structure themselves, the scientists turned to mice.
They implanted a disc-shaped open mold filled with dried bone powder under the skin of mice which was left to grow for 8 weeks. After surgical removal, the resultant bone was discovered to be remarkably similar to the natural spongy bone that houses bone marrow, and was crammed with blood cells. Further investigation also revealed that the cell composition of the marrow was identical to that of a mouse thighbone.
The team placed the marrow in a microfluidic device and managed to sustain it for about a week, which is usually a sufficient amount of time to conduct drug tests. When they exposed the marrow to radiation it became damaged as normal, however, when they applied a drug that is currently used to protect bone marrow cells from radiation, the engineered marrow was shielded from the damaging effects.
The scientists are hopeful that one day they may be able to use this technique to grow human bone marrow as a form of personalized medicine.
If you'd like to find out more, check out this video from the Wyss Institute: