Multilineage-differentiating stress-enduring cells attenuate the cognitive impairment caused by chronic cerebral hypoperfusion in rats

Abstract

Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic pluripotent- like stem cells that can migrate to damaged sites and contribute to tissue repair. Chronic cerebral hypoperfusion (CCH), which mimics vascular dementia, causes hippocampal neuronal degeneration and white matter (WM) damage, which lead to cognitive dysfunction. Currently, there are no effective treatments for it. We evaluated the efficiency of the human-Muse cell-based product CL2020 in treating CCH in rats. A bilateral common carotid artery occlusion was used to induce cognitive dysfunction. Six-weeks after carotid artery occlusion, CL2020 were injected intravenously. Cognitive function was assessed using a Barnes circular maze (BCM) at 3 weeks after CL2020 administration. Histological findings and western blots were assessed at 4 weeks after CL2020 administration. BCM assessment indicated recovery in cognitive function in the CL2020-treated group. Compared with the vehicle, CL2020 targeted the hippocampus, where it decreased neuronal loss and WM damage. CL2020 also promoted angiogenesis and suppressed apoptotic cell death. Western blotting of hippocampal samples revealed the downregulation of pro- apoptotic and the upregulation of anti-apoptotic proteins in the CL2020-treated group. In conclusion, intravenous administration of CL2020 improved the cognitive deficits caused by CCH, partly because of decreased hippocampal neuronal loss and WM damage, and increased angiogenesis in the hippocampus.