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Received Aug 24, 2017; Revised Dec 21, 2017; Accepted Jan 11, 2018
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Providing appropriate treatment to all stroke patients remains a genuine challenge. Sixteen million strokes occur every year [1], one every four minutes. Of these, 25% of patients die, 40% remain disabled, and 25% develop dementia. Stroke represents a considerable economic burden, with costs reaching 8.3 billion euros per year in France (Regional Health Agency report, 2013). Diabetes is a known independent risk factor for stroke, increasing its incidence threefold and worsening both the severity of the event and stroke-related mortality [2]. These observations are all the more alarming considering the anticipated doubling of the prevalence of diabetes by 2030 (World Health Organization, 2012).
Early recanalization following proximal cerebral artery occlusion is critical; stent retriever thrombectomy combined with recombinant tissue plasminogen activator (rtPA [Alteplase]) reduces disability at 90 days and improves functional independence when performed within 8 hours poststroke [3]. Nevertheless, the limited therapeutic time window and the scarcity of interventional neuroradiology centers mean that very few patients actually receive effective treatment. The search for strategies to extend the limited therapeutic window is challenging, particularly those focusing on restoring neurological damage.
Cell therapy-based approaches hold considerable promise. Translational research favors transplantation of autologous cells from various tissues and organs, in a more or less differentiated state. Expansion of mesenchymal stem cells requires several weeks of culture processing. In contrast, bone marrow-derived mononuclear cells (BM-MNC) can be obtained simply by density gradient centrifugation rendering them immediately ready for use. BM-MNC transplantation improves poststroke neurological deficit in rodents [4], and clinical trials have shown the feasibility of local [5], intra-arterial [6, 7], or intravenous [8, 9] administration. The underlying mechanisms are not fully understood: the transplanted cells show rare differentiation into endothelial or neural cells [10], but they do contribute to brain repair processes by stimulating endogenous angiogenesis [11], which in turn induces neurogenesis [12] and modulates the inflammatory response [13], thus counteracting the inflammatory cascade that creates a hostile environment compromising the survival of new cells.
Peripheral blood-derived MNC (PB-MNC) transplantation may be...