Neural stem cell transplantation in mouse model of juvenile neuronal ceroid-lipofuscinosis
RAJALA, TIINA (2008)
RAJALA, TIINA
2008
Biokemia - Biochemistry
Lääketieteellinen tiedekunta - Faculty of Medicine
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Hyväksymispäivämäärä
2008-05-14
Julkaisun pysyvä osoite on
https://urn.fi/urn:nbn:fi:uta-1-18150
https://urn.fi/urn:nbn:fi:uta-1-18150
Tiivistelmä
Background and Aims: This thesis investigates the suitability of neural stem cell transplantation in a mouse model of juvenile neuronal ceroid-lipofuscinosis (JNCL). JNCL is a childhood neurodegenerative disease leading to premature death in young adolescence. This hereditary disease has unfortunately no cure. Neural stem cells (NSCs) are under vigorous research for they have proven to be beneficial in many animal models of human disorders. This has been seen also in many lysosomal storage diseases, a group to which JNCL belongs. The aims of the thesis were to observe the survival, migration, and differentiation of NSC graft in the mouse model of JNCL.
Methods: GFP-expressing mouse neural stem cells were transplanted into 24 adult diseased mice and 24 wild type mice of the same strain. The cells were injected either into the cortex or the hippocampus and let to survive there for either one or four months. Control injections of PBS were performed on 48 mice. The differentiation capacity of the neural stem cells was analyzed by immunohistochemical stainings in vitro. Extensive microscopical analyses using endogenous fluorescence, immunohistochemistry, and Prussian blue stainings were performed to the brain sections. Relevant statistical analyses were done for the results.
Results: The survival rate of the transplanted cells was low in both diseased and wild type mice, ranging from 0 to 3 %. The transplanted cells were, however, able to survive for four months in the recipient brain with no statistical differences between the diseased mice and the wild type mice. The migration seemed not to be active, and the distribution of the cells was most prominent in the corpus callosum. The cells had the capability to produce neuron-like processes in vivo but did not show a clear differentiation profile.
Conclusions: The environment in the JNCL mouse model did not set limitations for the survival of the neural stem cells, and the cells were able to stay alive there for several months. However, a lot of optimization for the transplantation procedure needs to be done to accomplish better survival of the cells. With diminishing the early hostile reaction in the brain, the migration and differentiation of the cells will most likely become more active. As a conclusion, no reason is seen to avoid further testing of NSC transplantation in animal models of JNCL.
Asiasanat: Stem cells, neural stem cell, transplantation, JNCL, lysosomal storage disease, mouse model, histological analysis
Methods: GFP-expressing mouse neural stem cells were transplanted into 24 adult diseased mice and 24 wild type mice of the same strain. The cells were injected either into the cortex or the hippocampus and let to survive there for either one or four months. Control injections of PBS were performed on 48 mice. The differentiation capacity of the neural stem cells was analyzed by immunohistochemical stainings in vitro. Extensive microscopical analyses using endogenous fluorescence, immunohistochemistry, and Prussian blue stainings were performed to the brain sections. Relevant statistical analyses were done for the results.
Results: The survival rate of the transplanted cells was low in both diseased and wild type mice, ranging from 0 to 3 %. The transplanted cells were, however, able to survive for four months in the recipient brain with no statistical differences between the diseased mice and the wild type mice. The migration seemed not to be active, and the distribution of the cells was most prominent in the corpus callosum. The cells had the capability to produce neuron-like processes in vivo but did not show a clear differentiation profile.
Conclusions: The environment in the JNCL mouse model did not set limitations for the survival of the neural stem cells, and the cells were able to stay alive there for several months. However, a lot of optimization for the transplantation procedure needs to be done to accomplish better survival of the cells. With diminishing the early hostile reaction in the brain, the migration and differentiation of the cells will most likely become more active. As a conclusion, no reason is seen to avoid further testing of NSC transplantation in animal models of JNCL.
Asiasanat: Stem cells, neural stem cell, transplantation, JNCL, lysosomal storage disease, mouse model, histological analysis