In what my colleague labels “a classic case of bench-to-bedside research,” Stanford scientists and colleagues have discovered a possible reason for why tuberculosis frequently recurs years, or decades, after treatment: the ability of the disease to infiltrate and settle down in a particular class of stem cell in the bone marrow. As a result, the bacteria take advantage of the body’s own mechanisms of self-renewal.
The research, which was published today in Science Translational Medicine, focuses on a subset of stem cells in the bone marrow called mesenchymal stem cells. These cells can become several different types of specialized cells, including bone, fat and cartilage. Most often found in the bone marrow, the mesenchymal stem cells are known to be able to migrate to sites in the lungs, where the tuberculosis bacteria thrive. More from the release:
Not only did the scientists find genetic material from the bacteria inside the stem cells, they were also able to isolate active bacteria from the cells of human patients with tuberculosis who had undergone extensive treatment for the disease. The findings raise the possibility that other infectious agents may employ similar “wolf-in-stem-cell-clothing” tactics. And, although any new human treatments are likely to still be years away, they suggest a new possible target in the fight against tuberculosis, which infects nearly 2.2 billion people worldwide.
“We now need to learn how the bacteria find and infect this tiny population of stem cells, and what triggers it to reactivate years or decades after successful treatment of the disease,” said postdoctoral scholar Bikul Das, MBBS, PhD.
Looking forward, researchers intend to focus on examining the cellular mechanisms used by the tuberculosis bacteria to infect and persist in the mesenchymal stem cells, and how reactivation occurs on a molecular level. Beyond tuberculosis, their work could help identify other “microbial bad boy[s] that have learned how to exploit the stem cells’ properties as a perfect hiding place.”