title: Characterization of the secretome of human tooth germ stem cells (hTGSCs) reveals neuro-protection by fine-tuning micro-environment.
abstract: 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 β-amyloid peptide (β-AP) and 6-hydroxy-dopamine (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.
authors.affiliation: Center for Gene Therapy, Nationwide Children's Hospital, Ohio State University, 700 Children's Drive, Columbus, OH 43205, USA. mehmet.yalvac@nationwidechildrens.org
authors.forename: Mehmet Emir
authors.initials: ME
authors.lastname: Yalvaç
authors.forename: Aysen
authors.initials: A
authors.lastname: Yarat
authors.forename: Dilek
authors.initials: D
authors.lastname: Mercan
authors.forename: Albert A
authors.initials: AA
authors.lastname: Rizvanov
authors.forename: András
authors.initials: A
authors.lastname: Palotás
authors.forename: Fikrettin
authors.initials: F
authors.lastname: Şahin
mesh_terms: D000293:Adolescent; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D018925:Chemokines / Q000378:metabolism; D002648:Child; D016207:Cytokines / Q000378:metabolism; D004777:Environment; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008964:Molar, Third / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology; D009422:Nervous System Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D014083:Tooth Germ / Q000378:metabolism / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D018925:Chemokines; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins