Dormant, Chemotherapy-Resistant Stem Cells Discovered in the Intestines

Quiescent stem cells are dormant and are not impacted by cancer treatments.

New findings suggest that the intestine have a reservoir of chemotherapy-resistant stem cells that can be activated when needed, according to a study published by Cell Stem Cell. These drug-resistant passive stem cells (quiescent) may be involved with tissue regeneration, as well as tumor development.

The intestine has a high rate of regeneration due to the constant absorption of nutrients and waste elimination. The entire cell wall is regenerated every week, which explains why it holds numerous stem cells that can differentiate into various cells in the organ.

The authors said that the newly discovered cells are extremely different than known stem cells, because the newly found cells do not proliferate and are dormant, according to the study.

The quiescent cells are described as a reservoir of stem cells that have no apparent use under healthy conditions.

However, in stressful situations, such as after chemotherapy, during infections, or during inflammatory processes, the dormant cells play an important role. During these conditions, normal stem cells become depleted, but the quiescent cells can regenerate the population of normal cells, according to the study.

The authors believe that this discovery shows the complex, and largely unknown, nature of stem cell biology, which does not follow the typical model of cell organization.

"In intestinal cell hierarchy, there are no cells above others, so the 2 populations are in a continual balance to ensure the proper function of the organ,” said researcher Eduard Batlle, PhD.

A majority of current cancer drugs also have an effect on cell division in other tissues.

“Because quiescent stem cells divide infrequently, they are resistant to many types of chemotherapy and they regenerate the tissue that this treatment has damaged," Dr Batlle said.

Quiescent cells are present in numerous different types of tissues. Although they are involved with tissue regeneration, there is much evidence that the cells can also be important for cancer growth. Due to the advanced knowledge about intestinal stem cells, specifically the quiescent population, investigators may create specific therapies that target cell mechanisms to prevent cancer growth.

"It is difficult to study these cells, mainly because they are scarce and there are technical limitations with respect to monitoring, straining and distinguishing them from the others," said first author Francisco Barriga, PhD.

Over a period of 6 years, the authors used genetic tracing of cell lineages and transcriptomic analysis of individual cells to discover the unique genetic program used by quiescent stem cells and how it differs from other intestinal stem cells.

The authors have labeled the population using the Mex3a protein as a specific marker, which let them track the cells over time.

"We intend to continue studying quiescent stem cells in health and disease and to discover the function of the genes that distinguish them in the colon and in other organs," Dr Batlle concluded.