Monday, 4 February 2013

EGF boosts stem cell recovery after radiation therapy

Researchers from the Duke University Medical Center (DUMC) have discovered that the epidermal growth factor has a beneficial impact on the recovery of hematopoietic stem cells following exposure to radiation. These new findings could be employed to help cancer victims recovering from radiation treatment or people who have suffered radiation injuries, for example the ones that received high doses of radiation during the nuclear accident of 2011, in Japan.

Epidermal growth factor (EGF) is a growth protein stimulating cell growth, proliferation, and differentiation of various cells. The DUMC study focuses on what was initially thought to be an anomaly in a group of genetically modified mice. The observation was that these mice exhibited higher and unexplained resistance to radiation damage, something which the researchers decided to further investigate.

The mice mentioned before, lacked of two genes that are responsible for regulating the death of endothelial cells, the cells forming the endothelium tissue lining the inner surface of blood and lymphatic vessels. It was shown that these mice exhibited higher resistance to radiation compared to normal mice, thus increasing their survival ratio. The mice where then examined and found to have, up to 18 times, higher amounts of EGF in the bone marrow.

The DUMC researchers then tested if EGF had the potential to spur new growth of HSCs in bone marrow treated with radiation. The results were positive as a significant increase of HSCs was observed.

The research team continued their study with three mice groups. All groups were treated with radiation and were given a bone marrow transplant:
  • The first group received a hematopoietic stem cell transplant from healthy donors
  • The second group received a hematopoietic stem cell transplanlt from donors that were previously irradiated and treated with EGF
  • And the third got a bone marrow transplant from irradiated donors that were treated with saline

A human hematopoietic stem cell transplant

In the first group, the HSCs proliferated as expected, giving the best results (highest engraftment ratio). However the engraftment ratio in the second group was 20 times higher than the third group!

Additional experiments showed that the EGF can greatly increase the survival ratio after receiving lethal doses of radiation. Specifically, mice that were immediately treated with EGF after radiation exposure had a 93 % chance of survival, whereas the same ratio was only 53 % for the control group.

John Chute, senior author of the study, said that this is the first time a study shows that EGF promotes HSCs recovery following a radiation injury. According to him, the EGF treatment works by inhibiting the PUMA protein, which normally induces stem cell death after exposure to radiation.

Reference
Doan, P., Himburg, H., Helms, K., Russell, J., Fixsen, E., Quarmyne, M., Harris, J., Deoliviera, D., Sullivan, J., Chao, N., Kirsch, D., & Chute, J. (2013). Epidermal growth factor regulates hematopoietic regeneration after radiation injury Nature Medicine DOI: 10.1038/nm.3070

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