2026-06-01T11:52:45Zhttps://riuma.uma.es/rest/oai/requestoai:riuma.uma.es:10630/84762026-02-03T11:49:39Zcom_10630_2254col_10630_37959
RIUMA. Repositorio Institucional de la Universidad de Málaga
author
Páez-González, Patricia
2014-11-25T11:59:21Z
2014-11-25T11:59:21Z
2014-11-25
http://hdl.handle.net/10630/8476
Patricia Paez-Gonzalez
Kuo Lab, Dept. of Cell Biology, Duke University Medical Center, NC,USA.
Date: 11/16/2014
Utilizing stem cells in the adult brain hold great promise for regenerative medicine. Harnessing
ability of adult neural stem cells (NSCs) to generate new neurons or other types of brain cells may
provide much needed therapies for patients suffering from brain injuries or neuro-degenerative
diseases such as Parkinson’s, Scizophrenia, or Alzheimer’s disease. However, the treatments that
involve stem cells are based in NSC transplantation and its efficiency is really low.
The major barriers-to-progress in this area of research are immune-rejection of the implanted
cells, faulty tumorogenic growth, but mainly, a faulty integration of the improper progeny. To avoid the
problems that accompany NSC transplantation, we wanted to explore whether a new approach focused
on “modulating” the brain’s own resident stem cells to produce the appropriate cells after brain damage
was possible. In order to determine if “in situ” stem cell therapy was plausible, we first had to determine
whether 1)
Environment provides the right signals for the proper NSC function and generation of the
appropriate progeny, 2) whether in vivo NCSs are capable to elaborate an appropriate response under
different brain requirements, and 3) whether directed modulation of Neural Stem Cells function is
possible.
We found that using genetic alteration in only the neighboring ependymal cells has the profound
impact of nearly eliminating new neuron production in the lateral ventricular neurogenic region.
Secondly, we determined that cortical strokes that do not impact the neurogenic region induce
production on TSP4+ astrocytes that migrate to the injury site to produce the scar that stops cortical
bleeding. Thirdly, we have identified a novel cholinergic circuit that resides in the neurogenic region,
and that optogenetic stimulation or silencing of acetylcholine neurons can robustly up or down-regulate
new neuron production. These three discoveries have met the required conditions for using intrinsic
NSCs as therapy for brain regeneration and repair. I am now extending this line of research to
determine if this therapy is now a feasible technique for brain repair understanding how the local brain
circuits are modified as the NSCs transition to an injury response and back to normal production
following recovery. Together these data suggest that therapies utilizing the bodies own intrinsic control
mechanisms for NSC regulation may soon provide much needed avenues for future therapies that are
unattainable with other methods.
spa
Células madre neurales
Neural activity control of neural stem cells and SVZ niche response to brain injury
conference output
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