Mechanisms of Improving the Neuroprotective Effects of Multipotent Stromal Cells after Co-Culturing with Neurons

摘要

We explored a possibility to maximally alleviate a negative impact of stroke by increasing the therapeutic potential of multipotent mesenchymal stromal cells (MMSC). To do that, we studied the intercellular communication between MMSC and neural cells under their co-cultivation in vitro. Co-cultivation of MMSC and neurons from rat cerebral cortex resulted in a cell contents transfer between cells. Evidence of intercellular exchange was obtained using cytoplasmic fluorescent probes. Thus, we showed that cytosol transfer occurs preferentially from neurons toward MMSC. On the other hand, we observed a reverse intercellular transport of mitochondria (from MMSC toward neural cells). Intravenous administration of MMSC in the post-ischemic period reduced the pathological consequences of stroke, which resulted in a decrease of cerebral lesion and a partial recovery of the neurological status. At the same time, MMSC co-cultured with neurons demonstrated more profound neuroprotective efficiency than the unprimed MMSC. The production of one of the most important neurotrophic factors, BDNF, was slightly increased in MMSC after co-cultivation, and the factor was redistributed in the cytoplasm. We conclude that intercellular communications between neural and stem cells improve the protective capacity of MMSC after stroke. This could be a possible approach to increasing the therapeutic efficiency of cell therapy of cerebral ischemia.