Neural Regeneration Research ›› 2013, Vol. 8 ›› Issue (13): 1190-1200.doi: 10.3969/j.issn.1673-5374.2013.13.004

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Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson’s disease?

Hyung Ho Yoon1, Joongkee Min1, Nari Shin2, Yong Hwan Kim3, Jin-Mo Kim4, Yu-Shik Hwang5, Jun-Kyo Francis Suh4, Onyou Hwang2, Sang Ryong Jeon1   

  1. 1 Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
    2 Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea
    3 Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN, USA
    4 Center for Bionics of Korea Institute of Science and Technology, Seoul, Korea
    5 Department of Maxillofacial Biomedical Engineering, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, Korea
  • Received:2012-12-21 Revised:2013-04-03 Online:2013-05-05 Published:2013-05-05
  • Contact: Sang Ryong Jeon, M.D., Ph.D., Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Pungnap-2 dong, Songpa-gu, Seoul 138-736, Korea, srjeon@amc.seoul.kr.
  • About author:Hyung Ho Yoon★, M.S.

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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.