3908 Current Pharmaceutical Design, 2009, 15, 3908-3916 1381-6128/09 $55.00+.00 © 2009 Bentham Science Publishers Ltd. Potential Role of Dental Stem Cells in the Cellular Therapy of Cerebral Ischemia Mehmet E. Yalvac 1,# , Albert A. Rizvanov 1,2,3,#,* , Ertugrul Kilic 1,4 , Fikrettin Sahin 1 , Marat A. Mukhamedyarov 5 , Rustem R. Islamov 6 and András Palotás 7, * 1 Department of Genetics and BioEngineering, College of Engineering and Architecture, Yeditepe University, 26 Austos Campus, Kayisdagi cad., Kayisdagi, 34755 Istanbul, Turkey; 2 Department of Genetics, Faculty of Biology and Soil Sciences, Kazan State University, ul. Kremlevskaya 18, R-420008 Kazan, Russia; 3 Core research laboratory, Kazan State Medical University, ul. Butlerova 49, R-420012 Kazan, Russia; 4 Department of Physiology, College of Medicine, Yeditepe University, 26 Austos Campus, Kayisdagi cad., Kayisdagi, 34755 Istanbul, Turkey; 5 Department of Physiology, Kazan State Medical University, ul. Butlerova 49, R-420012 Kazan, Russia; 6 Department of Histology, Cytology and Embryology, Kazan State Medical University, ul. Butlerova 49, R-420012 Kazan, Russia; 7 Asklepios-Med Bt. (private practice and research center), H-6722 Szeged, Kossuth Lajos sgt. 23, Hungary Abstract: Stem cell based therapies for cerebral ischemia (CI) utilize different cell sources including embryonic stem cells (ESCs), neural stem cells (NSCs), umbilical cord blood cells (UCBCs), mesenchymal stem cells (MSCs), and some immortalized cell lines. To date, experimental studies showed that all of these cell sources have been successful to some extent in attenuating the ischemic damage and improving functional recovery after brain injury. Bone marrow derived MSCs seem to be the most widely used and well characterized cell source, which can be also employed for autologous transplantation. Currently, there are two main theories behind the therapeutic effect of stem cell transplantation for treating CIs. The first concept is cell replacement theory in which transplanted stem cells differentiate into progenitor and specialized somatic cells to supersede dying cells. The other hypothesis is based on immuno-modulatory, neuro-protective and neuro-trophic abilities of stem cells which help reducing stroke size and increasing the recovery of behavioral functions. Recent studies focusing on alternative stem cell sources have revealed that dental stem cells (DSCs), including dental pulp stem cells (DPSCs) and dental follicle cells (DFCs) possess properties of MSCs and NSCs. They differentiate into neural linage cells and some other cell types such as osteocytes, adipocytes, chondrocytes, muscle cells and hepatocytes. This review is intended to examine stem cell therapy approaches for CI and emphasize potential use of DSCs as an alternative cell source for the treatment of brain ischemia. Keywords: Cerebral ischemia, dental stem cells, stem cell therapy. INTRODUCTION Citizens of most developed countries are at a high risk of several “diseases of the civilized world” (lifestyle diseases, or diseases of longevity), such as cancer, atherosclerosis, diabetes, Alzheimer’s disease, cerebro-vascular maladies, and several other degenerative conditions. Of the many neurological disorders, cerebral ischemia (CI) has recently become the 3 rd most common cause of death both in the European Union (EU) and in the USA [1, 2]. Stroke is a cerebro-vascular accident. In contrast to its hemorrhagic sub-type, ischemic stroke is a condition in which there is insufficient blood-flow to the brain to meet metabolic demand, leading to poor oxygen supply (cerebral hypoxia) and thus to the death of brain tissue (cerebral *Address correspondence to these authors at the Department of Genetics, Faculty of Biology and Soil Sciences, Kazan State University, ul. Krem- levskaya 18, R-420008 Kazan, Russia; Tel: +(7)(843)231-5182; E-mail: rizvanov@gmail.com; Asklepios-Med Bt, H-6722 Szeged, Kossuth Lajos sgt. 23, Hungary; Tel: +(36)(30)255-6225; E-mail: palotas@asklepios-med.eu # These authors contributed equally to this project and should be considered co-first authors. infarction) [3], and is usually caused by eg. thrombosis, embolism, or systemic hypo-perfusion, etc. Treatment of acute stroke involves re-canalization of the occluded cerebral blood vessels within hours after stroke attack by various medical (pharmacological) and/or interventional (surgical) modes. Treatment with thrombo-(or fibrino-)lysis with the use of recombinant tissue plasminogen activator (rt-PA), thrombectomy (angioplasty and/or stent- ing), as well as prevention with anti-platelet drugs, anti- coagulants, blood-pressure control, statins, and/or endar- terectomy, etc. may reduce mortality rate by alleviating and/or preventing damage [4]. However, these approaches are not effective in a large number of cases, and irreversible, persistent cerebral damage will ensue. Because regeneration of brain tissue is very much limited, induction of recovery and neuro-protection by new therapeutic strategies, including novel pharmacological techniques and cell-based methods, are highly demanded [5]. A great number of neuro-protective molecules that are thought to enhance recovery after stroke have been identified and studied in experimental models, however none of them was successful in clinical trials, and their pharmaco-therapeutical efficacy is also limited due to their problematic transport through the blood brain barrier (BBB), requesting innovative drug-delivery options.