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Regenerative medicine for Parkinson’s disease using differentiated nerve cells derived from human buccal fat pad stem cells

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Abstract

The purpose of this study was to evaluate the utility of human adipose stem cells derived from the buccal fat pad (hBFP-ASCs) for nerve regeneration. Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons. PD is a candidate disease for cell replacement therapy because it has no fundamental therapeutic methods. We examined the properties of neural-related cells induced from hBFP-ASCs as a cell source for PD treatment. hBFP-ASCs were cultured in neurogenic differentiation medium for about 2 weeks. After the morphology of hBFP-ASCs changed to neural-like cells, the medium was replaced with neural maintenance medium. Cells differentiated from hBFP-ASCs showed neuron-like structures and expressed neuron markers (β3-tubulin, neurofilament 200, and microtubule-associated protein 2), an astrocyte marker (glial fibrillary acidic protein), or dopaminergic neuron-related marker (tyrosine hydroxylase). Induced neural cells were transplanted into a 6-hydroxydopamine (6-OHDA)-lesioned rat hemi-parkinsonian model. At 4 weeks after transplantation, 6-OHDA-lesioned rats were subjected to apomorphine-induced rotation analysis. The transplanted cells survived in the brain of rats as dopaminergic neural cells. No tumor formation was found after cell transplantation. We demonstrated differentiation of hBFP-ASCs into neural cells, and that transplantation of these neural cells improved the symptoms of model rats. Our results suggest that neurons differentiated from hBFP-ASCs would be applicable to cell replacement therapy of PD.

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Acknowledgements

We would like to thank Drs. Akihiro Ohyama and Junko Toyomura (Department of NDU Life Sciences, School of Life Dentistry, The Nippon Dental University), Yoshiaki Ide and Noriko Tominaga (Department of Developmental and Regenerative Dentistry, School of Life Dentistry, The Nippon Dental University), Minako Fukazawa and Miyuki Kawakami (Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Niigata, The Nippon Dental University) for providing their invaluable comments and technical support. We would also like to thank Professor Taka Nakahara (Department of Developmental and Regenerative Dentistry, School of Life Dentistry, The Nippon Dental University) for helpful discussion. We also thank Professor Yukio miyagawa (Developmental Science of Oral Biomaterials, School of Life Dentistry at Niigata, The Nippon Dental University) who provided knowledge and profitably suggestions for statistical analysis. We are also grateful to Dr. Toshiaki Tachibana (Division of Fine Morphology, Core Research Facilities, The Jikei University School of Medicine), who provided guidance for electron microscopy.

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Correspondence to Haruka Takahashi.

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No competing financial interests exist. The authors declare that there are no conflicts of interest related to the publication of this study.

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Takahashi, H., Ishikawa, H. & Tanaka, A. Regenerative medicine for Parkinson’s disease using differentiated nerve cells derived from human buccal fat pad stem cells. Human Cell 30, 60–71 (2017). https://doi.org/10.1007/s13577-017-0160-3

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