Tsupykov O. Effect of stem cell transplantation on the processes of nervous tissue regeneration after ischemic brain injury

We investigated the effect of stem cells transplantation on the regeneration of nervous tissue and behavioral phenomena on different models of cerebral ischemic injury in both adults and newborns. It has been shown that transplanted fetal GFP-positive neural progenitor cells (NPCs) able to migrate to damaged region of the CA1 hippocampal area, to differentiate both in astrocytes and in mature neurons that form synaptic contacts with host neurons. We demonstrated that global short-term cerebral ischemia resulted into cognitive impairments in mice. Stereotaxic transplantation of NPCs promoted the cognitive function recovery in experimental animals after ischemic brain injury. On the developed in vitro model of periventricular leukomalacia (PVLmiv) we showed that the presence of multipotent mesenchymal stromal cells (MMSCs) in the non-contact co-culture of brain slices diminished PVLmiv effects improving cell viability, preventing degradation of oligodendocytes and extensive astro- and microgliosis in brain slices. Our data suggest that protective capacity of MMSCs can be executed distantly most likely via released biomodulatory compounds.We showed that FGF-2-transduced progenitors grafted in the early postnatal rat cortex h ave the distinct tendency to associate with the vasculature and establish multiple proliferative clusters in the perivascular environment. Our data provide evidence that engineering neural progenitors to overexpress FGF-2 may be a suitable strategy to improve the integration of grafted neural progenitor cells with the host vasculature thereby generating neurovascular clusters with a neurogenic potential for brain repair. For the first time, we showed that extracellular matrix metalloproteinase inducer (EMMPRIN) overexpressing SVZ cells invade the injured cortical tissue more efficiently than controls. Our results suggest that EMMPRIN overexpression could be suitable approach to improve capacities of endogenous or transplanted progenitors to invade the injured cortex. For the first time, we demonstrated that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex.