August 11, 2010 ─ (BRONX, NY) ─ Scientists at Albert Einstein College of Medicine of Yeshiva University have received a five-year, $10.8 million grant to develop stem cell-based therapies that could be used to mitigate radiation-induced gastrointestinal syndrome – part of acute radiation syndrome (ARS) – for military personnel, first responders and the general public. The Einstein research, funded by the federal Centers for Medical Countermeasures Against Radiation, is part of a program coordinated by the National Institute of Allergy and Infectious Diseases.
"This type of research fills a special need," said lead investigator Chan dan Guha, M.B.B.S., Ph.D., professor and vice chair of radiation oncology at Einstein and Montefiore Medical Center. "Currently, post-event strategies for responding to ARS must be carried out within the first several hours of an event, and those strategies have demonstrated only marginal protection." At present, there are no Food and Drug Administration (FDA)-approved treatments that can effectively treat ARS. For first responders and others, this lack of protection against the effects of radiation could be fatal.
Radiation protection is a natural research avenue for Dr. Guha and his radiation oncology colleagues. Killing cancer cells with radiation therapy or chemotherapy must be done in ways that minimize toxicity to the rest of the body.
"When radiation is used in combination with chemotherapy for head and neck cancer or cervical cancer, it is very successful," said Dr. Guha. "But the same cannot be done for cancers in the abdomen. High doses of radiation cannot be administered effectively to that area because radiation is very toxic to the intestines and the liver. This is the same sort of toxicity that occurs in radiation-induced gastrointestinal syndrome."
Radiation to the abdomen can cause intestinal cells to begin dying within hours. The result is a loss of the intestine's protective mucosal lining, microbial infection, septic shock, and an inflammatory response that affects the entire body. Death is dose dependent and can occur within days following exposure.
In earlier research, Dr. Guha has shown that animals receiving lethal doses of radiation to their abdomen can be rescued by intravenous transplantation of bone marrow-derived stromal cells. Using their bone marrow-derived stem cell transplant technique, Einstein scientists have saved animals exposed to a radiation dose of 18-20 Gy ─ equal to more than 2.5 times their lethal dose. The transplant was successful in saving these animals from fatal radiation injury even when administered 24 hours after radiation exposure. This cell therapy is believed to create conditions that allow irradiated intestinal stem cells to recover.
The new grant will allow Einstein researchers to develop their bone marrow transplant technique with the goal of saving people suffering from radiation-induced gastrointestinal failure. Further research will be performed to identify chemical agents that accelerate repair and regeneration of stem cells exposed to irradiation.
A small portion of the grant will fund the work of Dr. William Fleming, M.D., Ph.D., of the Oregon Health & Science University, Portland, OR. He will look at treating radiation-induced bone marrow syndrome with endothelial progenitor cells. The grant also supports core facilities at Einstein for histopathology (Rani Sellers, Ph.D.) and metabolomics (Erwin Kurland, M.D. Ph.D.) and Stony Brook University Medical Center, Stony Brook, NY for proteomics (Emily Chen, Ph.D.) to support the work of Drs. Guha and Fleming.