Thursday, 31 January 2013

Stem cells act as a shelter for tuberculosis bacteria

In a new study, that also included humans, researchers from the Stanford University explain why tuberculosis is such a persistent infection, commonly recurring many years or even decades after being successfully treated. According to them, tuberculosis bacteria hijack the body's stem cells lying dormant, waiting there silently to attack once again..

It is a known fact that mesenchymal stem cells (MSCs) have a natural resistance to drug treatments and attacks from immune-system cells. This is why some types of cancer have a high recurrence ratio. According to the study, Mycobacterium tuberculosis bacteria take advantage of this property to turn it against their host. During their experiments, the researchers not only extracted genetic material from infected MSCs but whole, fully-functioning bacteria!

Bikul Das, the study's leading author, says that more than 15 years ago, while treating patients with tuberculosis in India, he accidentally noticed that tuberculosis bacteria were present in bone marrow tissue. This is was a total surprise for him and gave him an idea on why the infection is so persistent.

Das decided to test his hypothesis when he arrived in Stanford University as a postdoctoral scholar . First, he arranged a small experiment, in which he exposed human mesenchymal stem cells to M. tuberculosis bacteria. He discovered that the bacteria not only successfully invaded the MSCs but also had the capacity to survive inside them for at least a period two weeks.
Further experimentation exhibited that M. tuberculosis bacteria prefer to infect MSCs that express the CD271 cell surface marker. This small study also showed that the bacteria's viability was greatly reduced if the MSCs were induced to differentiate into another more specialised cell.

Mycobacterium tuberculosis bacteria

The next step was experimenting on a mouse model. Das used a manipulated strain of the infection created by researchers from the Cambridge University to infect his mice. The strain in question only activates in the presence of streptomycin (an antibiotic drug), staying dormant in its absence. 

After 6 months of streptomycin withdrawal Das extracted mesenchymal stem cells from the mice and found out that CD271 MSCs contained dormant bacteria. He then cultured these MSCs and transplanted them (via injection) to another group of healthy mice which in return were also infected.

The final step was to discover if the bacteria act similarly in a human model. For this, Das contacted collaborators in India who run a small clinical trial for him. During the trial, bone marrow biopsies (containing MSCs) were taken from 9 patients that had previously received full treatment for Tuberculosis. All patients were negative for bacterial presence in the sputum.

The researchers did however detect Tuberculosis DNA in the MSCs of 8 patients and successfully extracted whole dormant bacteria in 2 of them.

Das and his colleagues now plan to investigate how the bacteria initially infects stem cells and what causes them to reactive years or even decades later.


Tuberculosis (MTB, or TB) is a very common infectious disease leading in many cases to death. Various myobacteria may cause the disease, but in most cases it is caused by  Mycobacterium tuberculosis. It is estimated that about one third of the total population has been infected, however the distribution is not uniform. In many Asian and African countries more than 80 % test positive for the infection whereas the ratio in the U.S. is only 5-10 %
Some common symptoms of tuberculosis include:
  • Fever
  • Chronic cough with blood-tinged sputum
  • Night sweats
  • Weigh Loss
Educational video about the condition


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Reference
Stanford University Medical Center (2013, January 30). Tuberculosis may lurk in bone marrow stem cells of infected patients.

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