Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson's disease? |
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| Authors: | Hyung Ho Yoon Joongkee Min Nari Shin Yong Hwan Kim Jin-Mo Kim Yu-Shik Hwang Jun-Kyo Francis Suh Onyou Hwang Sang Ryong Jeon |
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| Institution: | Hyung Ho Yoon (Department of Neurological Surgery,Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea)； Joongkee Min (Department of Neurological Surgery,Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea)； Nari Shin (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea)； Yong Hwan Kim (Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN, USA)； Jin-Mo Kim (Center for Bionics of Korea Institute of Science and Technology, Seoul, Korea)； Yu-Shik Hwang (Department of Maxillofacial Biomedical Engineering, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, Korea)； Jun-Kyo Francis Suh (Center for Bionics of Korea Institute of Science and Technology, Seoul, Korea)； Onyou Hwang (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea)； Sang Ryong Jeon (Department of Neurological Surgery,Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea)； |
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| 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. 18F]-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. |
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| Keywords: | neural regeneration stem cells cell transplantation glucose metabolism human brain-derived neural stem cells human dental papilla-derived stem cells Parkinson''s disease positron emission tomography grants-supported paper neuroregeneration |
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