May 05, 2014 This is a microscopic view of the engineered bone with an opening exposing the internal trabecular bony network, overlaid with colored images of blood cells and a supportive vascular network that fill the open spaces in the bone marrow-on-a-chip. Credit: Harvard's Wyss Institute

The latest organ-on-a-chip from Harvard's Wyss Institute for Biologically Inspired Engineering reproduces the structure, functions and cellular make-up of bone marrow, a complex tissue that until now could only be studied intact in living animals, Institute researchers report in the May 4, 2014, online issue of Nature Methods. The device, dubbed "bone marrow-on-a-chip," gives scientists a much-needed new tool to test the effects of new drugs and toxic agents on whole bone marrow.

Specifically, the device could be used to develop safe and effective strategies to prevent or treat radiation's lethal effects on bone marrow without resorting to animal testing, a challenge being pursued at the Institute with funding from the U.S. Food and Drug Administration (FDA). In an initial test, the engineered bone marrow, like human marrow, withered in response to radiation unless a drug known to prevent radiation poisoning was present.

The bone marrow-on-a-chip could also be used in the future to maintain a cancer patient's own marrow temporarily while he or she underwent marrow-damaging treatments such as radiation therapy or high-dose chemotherapy.

"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 Don Ingber, M.D., Ph.D., Founding Director of the Wyss Institute, Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences, and senior author of the paper.

Ingber leads a large effort to develop human organs-on-chipssmall microfluidic devices that mimic the physiology of living organs. So far Wyss Institute teams have built lung, heart, kidney, and gut chips that reproduce key aspects of organ function, and they have more organs-on-chips in the works. The technology has been recognized internationally for its potential to replace animal testing of new drugs and environmental toxins, and as a new way for scientists to model human disease.

To build organ chips, in the past Wyss teams have combined 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 they needed a new approach to mimic organ function.

This video is not supported by your browser at this time.

This complexity arises because bone marrow has an integral relationship with bone. Marrow sits inside trabecular bonea solid-looking type of bone with a porous, honeycombed interior. Throughout the honeycomb, conditions vary. Some areas are warmer, some cooler; some are oxygen-rich, others oxygen-starved, and the dozen or so cell types each have their own preferred spots. To add complexity, bone marrow cells communicate with each other by secreting and sensing a variety of biomolecules, which act locally to tell them whether to live, die, specialize or multiply.

Rather than trying to reproduce such a complex structure cell by cell, the researchers enlisted mice to do it.

Follow this link:
Bone marrow-on-a-chip unveiled

Comments are closed.