Capturing complexity: Modeling bone marrow on a chip

Bone marrow on a chip organs on chips Wyss Institute Donald Ingber
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. (James Weaver, Harvard's Wyss Institute)

We’ve had a lung on a chip, and a gut on a chip. Now researchers at the Wyss Institute for Biologically Inspired Engineering have added another tissue to their list of “organs-on-chips”— devices that mimic in vitro tissues’ in vivo structure and function for pharmaceutical discovery and testing. In a paper published in Nature Methods, a team led by Donald Ingber, MD, PhD, (a member of Boston Children’s Hospital’s Vascular Biology Program and founding director of the Wyss), announced that they have developed “bone marrow-on-a-chip.”

The sheer complexity of the new device sets it apart from the Wyss’s previous organs, reflecting the greater natural complexity of bone marrow. As Wyss staff report in a press release:

[B]one marrow has an integral relationship with bone. Marrow sits inside trabecular bone—a 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.

So how do you fabricate something so complex? You provide the raw materials, then let nature take over—in this case, letting mice do the work:

[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 eight weeks, the research team removed the device from the animal and plugged it into a system that kept the newly grown marrow fed and oxygenated. They then used the device to test the toxicity and effectiveness of a drug designed to combat the effects of radiation on bone marrow, establishing the system’s potential utility as a drug development tool.

Bone marrow on a chip organs on chips Wyss Institute Donald Ingber
The disc-shaped trabecular bone fits into this microfluidic “chip,” and the marrow inside the bone is bathed in circulating fluids that nourish it, remove its waste and export newly made blood cells. (Harvard’s Wyss Institute)

The research team envisions a broad range of applications for the technology:

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.

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.

Read the full story at the Wyss Institute.