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UC Irvine study finds safer stem cell-derived therapy for brain radiation recovery

Microvesicle injections restored cognition without adverse side effects


Charles Limoli, PhD, UC Irvine professor of radiation oncology, leads study on treatment to improve cognition after brain radiation treatment.Irvine, Calif., April 7, 2016 — While stem cells have shown promise for treating brain regions damaged by cancer radiation treatments, University of California, Irvine researchers have found that microscopic vesicles isolated from these cells provide similar benefits without some of the risks associated with stem cells.

In research with rats, these membrane structures secreted by cells — called microvesicles — transplanted two days after cranial irradiation restored cognitive function, reduced inflammation and protected neurons, as measured in four- and six-week assessments — and with no sign of immunorejection or tumor growth, two stem cell-related risk factors.

Results of the study — led by Charles Limoli, PhD, professor of radiation oncology — appear this week in the early online edition of Proceedings of the National Academies of Science.

Microvesicles are small, fluid-filled sacs secreted by all human cells. Their plasma contains a range of bioactive cargo (proteins, RNAs, etc.) that can benefit cellular physiology. In the brain, they help regulate the health and functionality of neurons. Microvesicles also can play an important role in tissue regeneration.

Radiotherapy for brain tumors is limited by how well the surrounding tissue tolerates the treatment. Patients receiving radiation at effective levels suffer varying degrees of learning and memory loss that can adversely affect their quality of life.

"In almost every instance, people experience severe cognitive impairment that’s progressive and debilitating," Limoli said. "Pediatric cancer patients can experience a drop of up to three IQ points per year."

For the UC Irvine research, Limoli and colleagues isolated and removed microvesicles secreted by multipotent human neural stem cells. Through a series of injections in areas above the hippocampus — a region known for the growth of new neurons — microvesicles were transplanted into the brains of rats that had undergone radiation treatment. Each injection contained 2 microliters of microvesicles.

Starting one month after irradiation, the rodents receiving microvesicle injections showed significant improvements in cognition as gauged by four independent behavioral tasks. Limoli said these cognitive benefits were associated with considerable reductions in neuroinflammation and the preservation of neuronal structures — both classic signs that radiation injury in the brain was either prevented or reversed.

Limoli reported similar results from a 2011 study in which multipotent human neural stem cells were used. However, stem cells may present certain risks, such as rejection by the body’s immune system, altering the growth of existing tumors or forming into teratomas — conditions that are less problematic with microvesicles.

"The appeal of strategies using microvesicles instead of stem cells is that they eliminate any concerns for teratoma formation and substantially minimize side effects associated with immunorejection," Limoli said.

Limoli said further work is needed to identify specific factors within microvesicles that are responsible for the neuroprotective effects and to determine how long these beneficial effects persist.

Contributors to the study include Janet Baulch, Munjal Acharya, Barrett Allen, Ning Ru, Nicole Chmielewski, Erich Giedzinski, Amber Syage, Audrey Park, Sarah Benke and Vipan Parihar of the UC Irvine School of Medicine's Department of Radiation Oncology. The work received support from the Defense Threat Reduction Agency, the American Cancer Society, NASA, the National Institutes of Health and the UC Irvine Institute for Clinical & Translational Science.

For more information, contact:
Tom Vasich
UC Irvine Strategic Communications
949-824-6455
tmvasich@uci.edu

About the University of California, Irvine: Currently celebrating its 50th anniversary, UC Irvine is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, the university has more than 30,000 students and offers 192 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $4.8 billion annually to the local economy. For more about UC Irvine, visit www.uci.edu.

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