Bone Marrow-on-a-Chip Developed to Test Drug Effects

Researchers f rom Harvard’s Wyss Institute for Biologically Inspired Engineering have reproduced the structure, functions, and cellular make-up of bone marrow, to create a device known as “bone marrowon-a-chip.” The device could give scientists a tool to test the effects of new drugs and toxic agents on whole bone marrow. 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 of a mouse’s back. After eight weeks, the disk-shaped bone that had formed in the mold was surgically removed and examined with a CAT scanner. The scan showed a honeycomb-like structure that looked identical to natural trabecular bone. When the stained tissue was examined under a microscope, the marrow was packed with blood cells, just like marrow from a living mouse. In addition, when the researchers sorted the bone marrow cells by type, 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 steadily supplied nutrients and removed waste to mimic the circulation the tissue would experience in the body. Marrow in the device remained healthy for up to one week, long enough to test the toxicity and effectiveness of a new drug. Similar to marrow from live mice, this engineered marrow was also susceptible to radiation, but an FDA-approved drug that protects irradiated patients also protects the marrow on the chip. According to the study, 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. Bone marrow-on-a-chip could also be used to maintain a cancer patient’s own marrow temporarily while undergoing marrow-damaging treatments. The report is featured in the May 2014 online issue of Nature Methods.