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      Poststroke Cell Therapy of the Aged Brain

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          Abstract

          During aging, many neurodegenerative disorders are associated with reduced neurogenesis and a decline in the proliferation of stem/progenitor cells. The development of the stem cell (SC), the regenerative therapy field, gained tremendous expectations in the diseases that suffer from the lack of treatment options. Stem cell based therapy is a promising approach to promote neuroregeneration after brain injury and can be potentiated when combined with supportive pharmacological drug treatment, especially in the aged. However, the mechanism of action for a particular grafted cell type, the optimal delivery route, doses, or time window of administration after lesion is still under debate. Today, it is proved that these protections are most likely due to modulatory mechanisms rather than the expected cell replacement. Our group proved that important differences appear in the aged brain compared with young one, that is, the accelerated progression of ischemic area, or the delayed initiation of neurological recovery. In this light, these age-related aspects should be carefully evaluated in the clinical translation of neurorestorative therapies. This review is focused on the current perspectives and suitable sources of stem cells (SCs), mechanisms of action, and the most efficient delivery routes in neurorestoration therapies in the poststroke aged environment.

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          Most cited references50

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          Intravenous autologous bone marrow mononuclear stem cell therapy for ischemic stroke: a multicentric, randomized trial.

          Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke.
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            Adipose-derived stem cells: Implications in tissue regeneration.

            Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) that are obtained from abundant adipose tissue, adherent on plastic culture flasks, can be expanded in vitro, and have the capacity to differentiate into multiple cell lineages. Unlike bone marrow-derived MSCs, ASCs can be obtained from abundant adipose tissue by a minimally invasive procedure, which results in a high number of cells. Therefore, ASCs are promising for regenerating tissues and organs damaged by injury and diseases. This article reviews the implications of ASCs in tissue regeneration.
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              Transplantation of cultured human neuronal cells for patients with stroke.

              Transplantation of cultured neuronal cells is safe in animal models and improves motor and cognitive deficits in rats with stroke. The authors studied the safety and feasibility of human neuronal cellular transplantation in patients with basal ganglia stroke and fixed motor deficits, including 12 patients (aged 44 to 75 years) with an infarct 6 months to 6 years previously (stable for at least 2 months). Serial evaluations (12 to 18 months) showed no adverse cell-related serologic or imaging-defined effects. The total European Stroke Scale score improved in six patients (3 to 10 points), with a mean improvement 2.9 points in all patients (p = 0. 046). Six of 11 PET scans at 6 months showed improved fluorodeoxyglucose uptake at the implant site. Neuronal transplantation is feasible in patients with motor infarction.
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                Author and article information

                Journal
                Neural Plast
                Neural Plast
                NP
                Neural Plasticity
                Hindawi Publishing Corporation
                2090-5904
                1687-5443
                2015
                11 August 2015
                : 2015
                : 839638
                Affiliations
                1Department of Functional Sciences, Center of Clinical and Experimental Medicine, University of Medicine and Pharmacy of Craiova, Petru Rares Street 2, 200349 Craiova, Romania
                2University Hospital Rostock, Gehlsheimer Street 20, 18147 Rostock, Germany
                3Biochemistry Department, University of Medicine and Pharmacy “Victor Babes”, Eftimie Murgu Street 2, 300041 Timisoara, Romania
                Author notes

                Academic Editor: Alexandre H. Kihara

                Article
                10.1155/2015/839638
                4548142
                fdba2bd8-24fc-49ff-af0b-82b6c55abf46
                Copyright © 2015 Aurel Popa-Wagner et al.

                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.

                History
                : 9 March 2015
                : 15 July 2015
                Categories
                Review Article

                Neurosciences
                Neurosciences

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