title: Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson's disease?
abstract: Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [(18)F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stem cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.
authors.affiliation: Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hyung Ho
authors.initials: HH
authors.lastname: Yoon
authors.affiliation: Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Joongkee
authors.initials: J
authors.lastname: Min
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Nari
authors.initials: N
authors.lastname: Shin
authors.affiliation: Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN, USA.
authors.forename: Yong Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Center for Bionics of Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Jin-Mo
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Maxillofacial Biomedical Engineering, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, Korea.
authors.forename: Yu-Shik
authors.initials: YS
authors.lastname: Hwang
authors.affiliation: Center for Bionics of Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Jun-Kyo Francis
authors.initials: JK
authors.lastname: Suh
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Onyou
authors.initials: O
authors.lastname: Hwang
authors.affiliation: Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sang Ryong
authors.initials: SR
authors.lastname: Jeon
keywords: Parkinson's disease; cell transplantation; glucose metabolism; grants-supported paper; human brain-derived neural stem cells; human dental papilla-derived stem cells; neural regeneration; neuroregeneration; positron emission tomography; stem cells