Characterization of the secretome of human tooth germ stem cells (hTGSCs) reveals neuro-protection by fine-tuning micro-environment

Bone-marrow-derived mesenchymal stem cells (MSCs) demonstrate neuro-protective effects in several disease models. By producing growth-factors, cytokines and chemokines, they promote survival of neurons in damaged brain areas. Alternative MSC sources, such as human tooth germ stem cells (hTGSCs), have been investigated for their neuro-protective properties. They ameliorate effects of neuro-toxic agents by paracrine mechanisms, however these secreted bio-active molecules are not yet characterized. Therefore, the current study aimed to provide a detailed analysis of the secretome of hTGSCs. Brain cells were exposed to various toxic materials, including Alzheimer's ß-amyloid peptide (ß-AP) and 6-hydroxydopamine (6-OHDA). When co-cultured with hTGSCs, the activity of a number of anti-oxidant enzymes (catalase, glutathione-s-transferase, glutathione-peroxidase, superoxide-dismutase) was increased and neuronal death/apoptosis was subsequently reduced. The composition of the secreted bio-active materials is influenced by various pre-existing factors such as oxygen and glucose deprivation and the age of cells (passage number). This report reveals for the first time that the neuro-protective secretome of hTGSCs and the micro-environment of cells have a mutual and dynamic impact on one another. © 2013 Elsevier Inc. Marmara Üniversitesi Ministry of Education and Science of the Russian Federation This study was made possible by the contributions of the Scientific Research Project Department of Marmara University (Istanbul, Turkey) (Project No. SAG-C-DRP-210311-0042), Department of Genetics at the Yeditepe University (Istanbul, Turkey) and by Asklepios-Med (Szeged, Hungary). RAA was funded by Russian Ministry of Science and Education Grant ( FCP 14.A18.21.0113 ), as well as the Federal Center of Collective Use and Pharmaceutical Research and Education Center, Kazan (Volga Region) Federal University, Kazan, Russia.