and Medicine for Seniors
Human stem cells restore cognitive
function after chemotherapy damage
First solid evidence that
transplantation of human neural stem cells can reverse chemo induced
damage of healthy tissue in the brain
16, 2015 - Human nerve system stem cell treatments are showing promise
for reversing learning and memory deficits after chemotherapy, according
to UC Irvine researchers.
In preclinical studies using
rodents, they found that adult stem cells transplanted one week after
the completion of a series of chemotherapy sessions restored a range of
cognitive functions, as measured one month later using a comprehensive
platform of behavioral testing. In contrast, rats not treated with stem
cells showed significant learning and memory impairment.
The frequent use of chemotherapy to
combat multiple cancers can produce severe cognitive dysfunction, often
referred to as "chemobrain," which can persist and manifest in many ways
long after the end of treatments in as many as 75 percent of survivors -
a problem of particular concern with pediatric patients.
"Our findings provide the first
solid evidence that transplantation of human neural stem cells can be
used to reverse chemotherapeutic-induced damage of healthy tissue in the
brain," said Charles Limoli, a UCI professor of radiation oncology.
Study results appear in the Feb. 15
issue of Cancer Research, a journal of the American Association
for Cancer Research.
Many chemotherapeutic agents used
to treat disparate cancer types trigger inflammation in the hippocampus,
a cerebral region responsible for many cognitive abilities, such as
learning and memory. This inflammation can destroy neurons and other
cell types in the brain.
Additionally, these toxic compounds
damage the connective structure of neurons, called dendrites and axons,
and alter the integrity of synapses - the vital links that permit
neurons to pass electrical and chemical signals throughout the brain.
Limoli compares the process to a tree being pruned of its branches and
Consequently, the affected neurons
are less able to transmit important neural messages that underpin
learning and memory.
"In many instances, people
experience severe cognitive impairment that's progressive and
debilitating," Limoli said. "For pediatric cancer patients, the results
can be particularly devastating, leading to reduced IQ, asocial behavior
and diminished quality of life."
For the UCI study, adult neural
stem cells were transplanted into the brains of rats after chemotherapy.
They migrated throughout the hippocampus, where they survived and
differentiated into multiple neural cell types. Additionally, these
cells triggered the secretion of neurotrophic growth factors that helped
rebuild wounded neurons.
Importantly, Limoli and his
colleagues found that engrafted cells protected the host neurons,
thereby preventing the loss or promoting the repair of damaged neurons
and their finer structural elements, referred to as dendritic spines.
"This research suggests that stem
cell therapies may one day be implemented in the clinic to provide
relief to patients suffering from cognitive impairments incurred as a
result of their cancer treatments," Limoli said. "While much work
remains, a clinical trial analyzing the safety of such approaches may be
possible within a few years."
Munjal Acharya, Lori-Ann Christie,
Vahan Martirosian, Nicole N. Chmielewski, Nevine Hanna, Katherine Tran,
Alicia Liao and Vipan Parihar of UCI contributed to the study, which was
funded by the National Institutes of Health (grant R01 NS074388581) and
supported by UCI's Institute for Clinical & Translational Science.
About the University of
California, Irvine: Currently celebrating its
50th anniversary, UCI 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, UCI 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 on UCI, visit