title: Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats.
abstract: Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model.
authors.affiliation: Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Müller
authors.affiliation: Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany.
authors.forename: Christiana
authors.initials: C
authors.lastname: Ossig
authors.affiliation: Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany.
authors.forename: Johannes F W
authors.initials: JF
authors.lastname: Greiner
authors.affiliation: Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hauser
authors.affiliation: Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Fauser
authors.affiliation: Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany.
authors.forename: Darius
authors.initials: D
authors.lastname: Widera
authors.affiliation: Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kaltschmidt
authors.affiliation: Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany barbara.kaltschmidt@uni-bielefeld.de Alexander.Storch@neuro.med.tu-dresden.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
authors.affiliation: Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany; Division of Neurodegenerative Diseases, Department of Neurology, and Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany; German Center for Neurodegenerative Diseases Dresden, Dresden, Germany; Cell Biology, University of Bielefeld, Bielefeld, Germany barbara.kaltschmidt@uni-bielefeld.de Alexander.Storch@neuro.med.tu-dresden.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kaltschmidt
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000637:transplantation; D000818:Animals; D002454:Cell Differentiation; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D009432:Neural Crest / Q000166:cytology / Q000637:transplantation*; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D020734:Parkinsonian Disorders / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods
keywords: Adult stem cells; Cell transplantation; Nasal stem cells; Neural differentiation; Parkinson's disease