최근 줄기세포에 신경보호 인자를 분비하게 조정하여 헌팅턴병 동물에 적용한 연구결과가 보고되었습니다. 동물에서는 많은 줄기세포 연구가 좋은 결과를 보이고 있으나 사람에 적용하는 것이 큰 해결과제로서 아직까지 큰 난제로 여겨집니다. 궁극적으로 줄기세포를 이용한 치료제 개발이 필요하고 많은 성과들이 보고 되고 있어, 현시점에서는 임상시험 단계에서 개발되고 있으나, 지금의 연구개발 성과를 고려 10-20년 뒤에는 줄기세포가 실제 치료제로 적용될 수 있는 전환점을 맞지 않을까 생각해 봅니다.
with Huntington's Disease Successfully Targeted by Human Stem Cells, UC
disease, a fatal neurodegenerative disease, is characterized by
progressive neuronal loss in the striatum, a brain area involved in
and behavioral control, followed by generalized brain atrophy.
neuron loss is responsible for some of the more serious
symptoms, such as impaired movement control, cognitive decline,
severe behavioral disorders. Brain-derived neurotrophic factor (BDNF),
to be reduced in Huntington's post-mortem human brains, is a promising
candidate for treatment of the disease, as it has been shown to prevent
death and to stimulate the growth and migration of brain cells in the
of mouse models.
stem cells (MSCs) have been shown to be effective in delivering
to mouse brains because they are not rejected by the immune system, as
may occur with viruses, and they are attracted to sites of injury,
other factors that reduce inflammation and enhance connection
neurons. However, the use of human MSCs in mouse models has been
by mouse immune systems, which rejects these foreign cells.
were now able to overcome these setbacks, advancing the
of the BDNF/MSC platform for clinical applications.
UC Davis team designed a system to immuno-suppress mouse models of
disease to successfully test the efficacy of BDNF delivery by
MSCs. First, researchers isolated MSCs from healthy human bone marrow
and engineered them to secrete elevated amounts of BDNF. The grown
of MSCs was then injected into the brains of Huntington's mouse
who were then tested weekly for behavioral changes and degeneration.
injected with MSCs, compared to those injected with a placebo, showed
less anxiety, a hallmark characteristic of Huntington's. In
mice treated with MSCs showed less degeneration in the striatum,
neuron growth activity, and an extended lifespan, by 15 percent,
pared with control mice.
results are an important step for researchers to get U.S. Food and
Administration approval to test the therapy's safety and efficacy in
patients with the disease. "For the first time, human stem cells have
successfully used as a platform to deliver brain-derived neurotrophic
(BDNF), the growth factor that shows great promise for treating
disease," principal investigator Prof. Vicki Wheelock said in a
release <http://www.ucdmc.ucdavis.edu/publish/news/newsroom/10872> .
must complete additional animal studies before we can apply for
approval to test this therapy in Huntington's patients, but the
we've seen using the human cell products in mouse models of the
are very encouraging."
Category: Cell Therapy
Mesenchymal Stem Cells Genetically Engineered to Overexpress
Neurotrophic Factor Improve Outcomes in Huntington's Disease
Huntington's disease (HD) is a fatal degenerative autosomal
neuropsychiatric disease that causes neuronal death and is
by progressive striatal and then widespread brain atrophy.
neurotrophic factor (BDNF) is a lead candidate for the
of HD, as it has been shown to prevent cell death and to stimulate
growth and migration of new neurons in the brain in transgenic mouse
BDNF levels are reduced in HD postmortem human brain. Previous
have shown efficacy of mesenchymal stem/stromal cells (MSC)/BDNF
murine MSCs, and the present study used human MSCs to advance the
potential of the MSC/BDNF platform for clinical application.
studies were performed to examine the effects of
transplanted human MSC/BDNF on disease progression in two
of immune-suppressed HD transgenic mice: YAC128 and R6/2. MSC/BDNF
decreased striatal atrophy in YAC128 mice. MSC/BDNF treatment also
reduced anxiety as measured in the open-field assay. Both MSC
MSC/BDNF treatments induced a significant increase in neurogenesis-like
in R6/2 mice. MSC/BDNF treatment also increased the mean lifespan
the R6/2 mice. Our genetically modified MSC/BDNF cells set a precedent
stem cell-based neurotherapeutics and could potentially be modified for
neurodegenerative disorders such as amyotrophic lateral sclerosis,
disease, and some forms of Parkinson's disease. These cells
a platform delivery system for future studies involving corrective