Reprogramming Stem Cells May Prevent Cancer after Radiation

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Mar 2, 2015

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After a human body is subjected to full body radiation, some faulty stem cells are left which re-engineer the blood system and enhances cancer risk in the person. A study at the University of Colorado center has revealed that this can be prevented by artificially activating s stem cell maintenance pathway.

The study was published in the journal Stem Cells. It says that our body has evolved some ways to get rid of faulty stem cells and one such way is a ˜program' that makes stem cells damaged by radiation differentiate into other cells that can no longer survive forever. Due to radiation, the stem cells lose their stemness and hence it doesn't make sense to have them around to remove damaged cells.

The study revealed that when the full body is irradiated, this same safeguard of “programmed mediocrity” that weeds out stem cells damaged by radiation allows blood cancers to grow. If we can reprogram this safeguard, we may have a way to prevent cancer after a body is subjected to radiation.

James DeGregori, PhD, investigator at the CU Cancer Center, professor of Biochemistry and Molecular Genetics at the CU School of Medicine, and the paper’s senior author said that human body has not evolved to deal with leaking nuclear reactors and CT scans. It can only manage a few cells at a time after receiving dangerous doses of radiation and other damages to its DNA.

DeGregori along with doctoral student Courtney Fleenor and colleagues explored the effects of full body radiation on the blood stem cells of mice. For this case radiation increased the probability that cells in the hematopoietic stem cell system would differentiate. It was seen that while most followed this instruction, there were a few that did not. It was observed that stem cells with a very specific mutation were able to disobey the instruction to differentiate and retain their “stemness”.

It is understood that genetic inhibition of the gene C/EBPA allowed a few stem cells to keep the ability to act as stem cells. With competition from other, healthy stem cells removed, the stem cells with reduced C/EBPA dominated the blood cell production system. Thus, the blood system transitioned from C/EBPA+ cells to primarily C/EBPA- cells.

Scientists have known that due to the occurrence of mutations and other genetic alterations which results in inhibition of the C/EBPA gene, acute myeloid leukemia in humans is caused. Hence, it was deduced that not mutations caused due to radiation, but a blood system reengineered by faulty stem cells which creates cancer risk in people are exposed to radiation.

DeGregori opined that when the healthy blood system is healthy, healthy stem cells out-compete stem cells that happen to have the C/EBPA mutation. However, when radiation reduces the fitness of the stem cell population, the mutated cells suddenly have the opportunity to take over.

DeGregori said that if one were working in a situation in which he was likely to experience full-body radiation, he would benefit from freezing a bunch of his HSCs. He further explained that an infusion of healthy HSCs after radiation exposure is likely allow the healthy blood system to out-compete the HSC with cancer-causing mutations.

These studies not only tell us why radiation makes hematopoietic stem cells (HSCs) differentiate; they also give us the knowledge that by activating a stem cell maintenance pathway, we can keep that from happening.