From University of South Florida Health Sciences Center
USF neuroscientists study potential of cord blood cells to rescue aging brain
$1.3-million NIA grant awarded
Tampa, FL (April 25, 2002) -- The University of South Florida Center for Aging and Brain Repair has been awarded a $1.3-million federal grant to study whether stem cells from human umbilical cord blood (HUCB) can rescue the brain from age-related decline.
Using an animal model, the 5-year, National Institute on Aging study will address critical questions about HUBC cells' true potential to successfully treat the normal mental declines of aging as well as neurodegenerative diseases.
Studies at USF and elsewhere have suggested that HUCB may be a noncontroversial and more readily available source of therapeutic cells for treating neurological diseases like Parkinson's or Alzheimer's disease and brain injuries such as stroke.
"We can change the destiny of a portion of these cells so that they take on the characteristics of neurons," said Tanja Zigova, PhD, principal investigator for the grant and assistant professor of neurosurgery at the Center for Aging and Brain Repair, USF College of Medicine.
"Our ultimate goal is to find out how to turn enough of them into specialized neurons that would read specific cues from the brain, migrate where we want them to go, and produce the types of neurotransmittters (chemical messengers) that must be replenished to restore brain function."
"One aspect of the research is to determine if the HUCB cells can be used to try to reverse age-related declines in learning and memory," said USF neuroscientist Paula Bickford, PhD, a co-investigator for the study. "If we observe such a change in aged rats, then perhaps it will be possible to use this approach for human aging. Clearly, there is a lot of work to be done before we take that step, and this award makes it possible for us to do that work."
Cord blood cells include a significant number of stem cells -- immature, unspecialized cells with the potential to become any cell in the body, including neurons. Researchers at the USF Center for Aging and Brain Repair were among the first to show that these cells can be reprogrammed in laboratory cultures to become immature nerve cells. They've also demonstrated that HUCB cells transplanted into the developing brains of neonatal rats begin to look like nerve cells and express certain proteins found only in neurons and glial cells.
Coaxing cells to resemble neurons is a big step. The much bigger and trickier hurdle is getting them to behave like neurons in the brain.
The USF study will use a model of aging rats to test the following:
- Which growth and nutritional factors best prompt malleable HUBC cells to follow pathways that lead the immature cells to become specific types of neurons.
- Whether the age of transplant recipients affects the ability of HUBC cells to grow and differentiate. The researchers want to know if the younger brain is a more conducive environment than the older brain for forming different types of neural tissue and promoting the reconnection of brain pathways. Using young, middle-aged and old rats, the researchers will transplant HUBC-derived cells into the subventricular region and hippocampus of the rodents' brains. These are the two areas of the brain where new neurons and glia are regenerated throughout life.
- Whether HUCB-derived cells transplanted directly into the brains of aging rats can reverse or slow age-related declines in learning and memory. In another experiment, the cells will be administered intravenously. The rats' ability to learn and their working memories will be tested using a water maze before and after transplant.
The researchers hope to discern whether any recovery stimulated by the HUCB cells is actually the result of replacing lost neurons or an indirect benefit of growth and nutritional substances, known as trophic factors, produced by the stem cells.
"The studies by Dr. Zigova should add greatly to our mission of developing non-embryonic stem cell therapies for brain repair," said Paul R. Sanberg, PhD, DSc, professor of neurosurgery and director of the Center for Aging and Brain Repair. "This will be the Center's first analysis of stem cells as a potential treatment for a condition that eventually affects everyone's brain -- aging."
The USF Center for Aging and Brain Repair is a leader in the search for novel cell therapies to combat Parkinson's disease, Huntington's disease, Alzheimer's, stroke and other neurodegenerative disorders, as well as spinal cord injury.