Transplantation of human cord blood-derived neural stem cells modify endogenous ischemia-induced neurogenesis in post-stroke rats

• Autorzy: Jablonska A. , Wojcik L. , Zalewska T. , Wanacka E. , Lukomska B.
• Języki publikacji: EN

Abstrakty

EN

Studies in experimental stroke demonstrate that cerebral ischemic injury promotes neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of the dentate gyrus. Spontaneously occurring injury-induced neurogenesis is insufficient to fully reverse disease pathophysiology. Exogenous neural progenitors transplanted into damaged brain might be useful for facilitating the repair of damaged tissue by instructing several endogenous processes. However, the molecular and cellular mechanisms stimulating cell proliferation and mediating the migration of arising neuroblasts towards the ischemic boundary still remain to be characterized. Building evidence suggests that matrix metalloproteinases (MMPs) seem to play a role in neurogenesis-associated processes, providing an environment which may be instructive or permissive to stem cells activation. The overall goal of our present studies was to examine whether HUCB-NSC transplantation modulates migration of endogenous progenitor cells and MMPs activity in adult rat brain after focal ischemia. Methods: 2x104 neural stem cells from human cord blood (HUCB-NSC) were transplanted into corpus callosum of naive or focally injured (induced by 1µl/50nmol OUA injection) rat brain. At 1, 3, 7 and 14 days rat brains were removed. Then immunocytochemical analysis of doublecortin (DCX) (marker expressed by immature migratory neuroblasts) and in situ zymography of MMPs activity was performed. Results: OUA-induced brain lesion resulted in increase of DCX+ cells in SVZ and SGZ in comparison to intact rats. This response has been potentiated by HUCBNSC transplantation. Moreover, the activation of MMPs in cells was visible in SVZ. At 7th day after HUCB-NSC transplantation the intense migration of DCX+ cells from SVZ towards ischemic boundary regions of the striatum was observed. Double-labeling showed co-localization of DCX marker with MMPs activity. The presence of MMPs appeared to be associated with cell nuclei and cytoplasm but interestingly it was also seen outside the cell bodies and in the neuronal protrusions. Conclusions: Proteolytic activity of MMPs in extracellular compartment suggests its ability to remodel extracellular matrix and facilitate migration of neuroblasts to the damaged brain areas. The localization of MMPs in cell nuclei implies the involvement of these proteases in proteolytical activation of pro-neural gene transcription. Supported by MSHE grant no N401 014235.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: 1
• Opis fizyczny: p.172-173

Twórcy

autor

Jablonska A.

• Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland

autor

Wojcik L.

• Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland

autor

Zalewska T.

• Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland

autor

Wanacka E.

• Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland

autor

Lukomska B.

• Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland