Transplants in Animal Models Could Translate into Therapy for Humans

(Philadelphia, PA) - Neural stem cells, transplanted into injured brains, survive, proliferate, and improve brain function in laboratory models according to research based at the University of Pennsylvania School of Medicine. The findings, published in the October edition of the journal Neurosurgery, suggest that stem cells could provide the first clinical therapy to treat traumatic brain injuries. Traumatic brain injuries occur in two million Americans each year and are the leading cause of long-term neurological disability in children and young adults.

"Transplantation of neural stem cells in mice three days after brain injury promotes the improvement of specific components of motor function," said Tracy K. McIntosh, PhD, professor in the Department of Neurosurgery, Director of Penn's Head Injury Center, and senior author of the study. "More importantly, these stem cells respond to signals and create replacement cells: both neurons, which transmit nerve signals, and glial cells, which serve many essential supportive roles in the nervous system."

If stem cells are blank slates, able to become any type of body cells, then neural stem cells (NSCs) are slates with the basics of neurology already written on them, waiting for signals in the nervous system to fill in the blanks. The NSCs used by McIntosh and his colleagues were cloned from mouse progenitor cells and grown in culture. The advantage of NSCs exists in their ability to easily incorporate themselves into their new environment in ways other types of transplants could not.

"If you put these cells into normal newborn mice, they would behave exactly like normal cells - they create different neural cell types and they don't reproduce tumorigenically," said McIntosh. "In humans, the use of similar neural stem cells would avoid the ethical dilemmas posed by fetal stem cells and the limitations seen in cultures of cloned neurons."

In humans, traumatic brain injury is associated with disabilities affecting mobility, motor function and coordination. Following NSC transplantation in mice, the researchers used simple tests to determine motor skills. They found that mice with transplanted NSCs recovered much of their physical ability. The transplanted NSCs, however, seemed to have little effect in aiding recovery of lost cognitive abilities.

"The ultimate goal, of course, is to translate what we have learned into a therapy for humans," said McIntosh. Neural transplantation has been suggested to be potentially useful as a therapeutic intervention in several central nervous system diseases including Parkinson's disease, Huntington's disease, ischemic brain injury, and spinal cord injury. While McIntosh is impressed with the results of NSC transplants in mice, similar trials for humans are not expected in the near future.

The lead author on this study is Peter Reiss, MD, a visiting fellow from the University of Cologne working in Dr. McIntosh's laboratory. Much of the work was performed in collaboration with the laboratory of Evan Y. Snyder, MD, Harvard Medical School.

Other contributing researchers from the Department of Neurosurgery include, Chen Zhang, MD, PhD, Kathryn E. Saatman, PhD, Helmut L. Laurer, MD, Luca G. Longhi, MD, Ramesh Raghupathi, PhD, Philipp Lenzlinger, MD, Jonathan Lifshitz, PhD, John Boockvar, MD, Grant Sinson, MD, and M. Sean Grady, MD. Contributing researchers from outside of Penn include Edmund Neugebauer, MD, of the University of Cologne, Germany and Yang D. Teng, MD, from Harvard Medical School.

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Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.

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