title: Dopaminergic-like neurons derived from oral mucosa stem cells by developmental cues improve symptoms in the hemi-parkinsonian rat model.
abstract: Achieving safe and readily accessible sources for cell replacement therapy in Parkinson's disease (PD) is still a challenging unresolved issue. Recently, a primitive neural crest stem cell population (hOMSC) was isolated from the adult human oral mucosa and characterized in vitro and in vivo. In this study we assessed hOMSC ability to differentiate into dopamine-secreting cells with a neuronal-dopaminergic phenotype in vitro in response to dopaminergic developmental cues and tested their therapeutic potential in the hemi-Parkinsonian rat model. We found that hOMSC express constitutively a repertoire of neuronal and dopaminergic markers and pivotal transcription factors. Soluble developmental factors induced a reproducible neuronal-like morphology in the majority of hOMSC, downregulated stem cells markers, upregulated the expression of the neuronal and dopaminergic markers that resulted in dopamine release capabilities. Transplantation of these dopaminergic-induced hOMSC into the striatum of hemi-Parkinsonian rats improved their behavioral deficits as determined by amphetamine-induced rotational behavior, motor asymmetry and motor coordination tests. Human TH expressing cells and increased levels of dopamine in the transplanted hemispheres were observed 10 weeks after transplantation. These results demonstrate for the first time that soluble factors involved in the development of DA neurons, induced a DA phenotype in hOMSC in vitro that significantly improved the motor function of hemiparkinsonian rats. Based on their neural-related origin, their niche accessibility by minimal-invasive procedures and their propensity for DA differentiation, hOMSC emerge as an attractive tool for autologous cell replacement therapy in PD.
authors.affiliation: Neurosciences Laboratory, Felsenstein Medical Research Center-Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Javier
authors.initials: J
authors.lastname: Ganz
authors.affiliation: Oral Biology Dept., School of Dental Medicine, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ina
authors.initials: I
authors.lastname: Arie
authors.affiliation: Oral Biology Dept., School of Dental Medicine, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Sigal
authors.initials: S
authors.lastname: Buch
authors.affiliation: Neurosciences Laboratory, Felsenstein Medical Research Center-Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Tali Ben
authors.initials: TB
authors.lastname: Zur
authors.affiliation: Neurosciences Laboratory, Felsenstein Medical Research Center-Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Barhum
authors.affiliation: Oral & Maxillofacial Dept., Baruch Padeh Medical Center, Poria, Lower Galilee, Israel.
authors.forename: Sammy
authors.initials: S
authors.lastname: Pour
authors.affiliation: Oral & Maxillofacial Dept., Baruch Padeh Medical Center, Poria, Lower Galilee, Israel.
authors.forename: Shareef
authors.initials: S
authors.lastname: Araidy
authors.affiliation: Oral Biology Dept., School of Dental Medicine, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Sandu
authors.initials: S
authors.lastname: Pitaru
authors.affiliation: Neurosciences Laboratory, Felsenstein Medical Research Center-Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Offen
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D003463:Cues; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology*; D006801:Humans; D008297:Male; D051379:Mice; D009061:Mouth Mucosa / Q000166:cytology*; D017072:Neostriatum / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000473:pathology* / Q000628:therapy*; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine