Recently, the design of new brain repair strategies based on stem cell transplantation has received a tremendous amount of attention.
This has been due to the increased incidence of neurodegenerative diseases and the absence of effective chemically based therapies. In this context the potential use of stem cells for transplantation appears as a promising alternative to restore lost cells (i.e. neurons or oligodendrocytes) in the central nervous system (CNS).
In this context, adult neural progenitors derived from olfactory neuroepithelium could constitute an excellent candidate.
Olfactory neuroepithelium is a unique source of adult human progenitors, which can be obtained from an individual without invasive surgery. These cells have the capacity to continually replace damaged neurons and glia throughout life; they can be amplified in vitro and create neurospheres and they can adopt a neuronal or glial fate depending on environmental factors. They survive, integrate and are functional when transplanted into a rat model of injured spinal cord.
We propose to further study olfactory neuroepithelium cells and to develop in vitro amplification and differentiation procedures to obtain a pure population of committed progenitors for transplantation into damaged CNS or for use in drug research, pharmacological evaluation and gene manipulation.
As a first step to use adult olfactory progenitors to facilitate CNS repair, we propose to test the capacity of these cells to differentiate into dopaminergic phenotype and investigate their restorative capacity when grafted into a denervated striatum.
Analogously, the potential of adult olfactory progenitors to differentiate into oligodendrocytic phenotype and to restore oligodendrocytes will be evaluated in hypomyelinated corpus callosum of mice affected by genetically determined myelinopathy (shiverer mice).
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