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Dental follicle cells show potential for treating Parkinson’s disease through dopaminergic-neuronogenic differentiation

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Abstract

Among all the adult stem cells, odontogenic stem cells inherit the characterization of neurogenic potential of their precursor ones–the cranial crest cells. Dental follicle cells (DFCs), one of the special kind of odontogenic stem cells, are raising interest in applying to regenerative medicine for they possess multi-differentiation potential, relatively free access and ethic-friendly characteristic. Parkinson’s disease (PD), as one of the common neurodegenerative disorders, affects about 0.3% of the general population. Stem cell therapies are thought to be effective to treat it. Aiming at tackling ethical-concernings, confined sources and practically applicational limits, we made use of dopaminergic neurongenic differentiation potential of the DFCs and dedicated every effort to applying them as promising cell source for treating PD. Dental follicle cells were cultured from human dental follicle tissues collected from 12 to 18-year-old teenagers’ completely impacted third molars. Our data demonstrated that hDFCs were expressing mesenchymal stem cell-associated surface markers, and possessed the ability of osteogenic, adipogenic and neurogenic differentiation in vitro. Additionally, hDFCs formed neuron-like cells in vitro and in vivo, as well as expressing dopaminergic-neuronogenic marker–TH. Moreover, hDFCs survived in the transplanted areas of the Parkinson’s disease model of mouse over six weeks post-surgery, and the number of TH-positive DFCs in the DFCs-Grafted group surpassed its counterpart of the MPTP group with statistically significant difference. This study indicated that hDFCs might be a promising source of dopaminergic neurons for functional transplantation, and encouraged further detailed studies on the potential of hDFCs for treating PD.

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The datasets supporting the conclusions of this article are included within the article.

Abbreviations

PD:

Parkinson’s disease

DPSCs:

Dental pulp stem cells

SHEDs:

Stem cells from exfoliated deciduous teeth

DFCs:

Dental follicle cells

SCAPs:

Stem cells from apical papilla

DPLSCs:

Dental periodontal ligament stem cells

BMSCs:

Bone marrow stromal cells

NCCs:

Neural crest cells

GFAP:

Glial fibrillary acidic protein

ESCs:

Embryonic stem cells

NSCs:

Neural stem cells

PBS:

Phosphate buffer saline

α-MEM:

Alpha type of modified Eagle’s medium

FBS:

Fetal bovine serum

DAPI:

4′,6-Diamidino-2-phenylindole

TH:

Tyrosine hydroxylase

SNc:

Substantia nigra compacta

GFP:

Green fluorescent protein

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

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Acknowledgements

This work is supported by National Key Research and Development Program of China (Nos. 2017YFA0104800), National Natural Science Foundation of China (31771062, 31971281), and Key Research and Development Program of Sichuan Province (2017SZ0031). The authors express their most grateful gratitude for the kindly support.

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Authors and Affiliations

  1. Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China

    Fei Bi, Jie Xiong, Xue Han, Chao Yang, Xinghan Li, Guoqing Chen, Weihua Guo & Weidong Tian

  2. National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China

    Fei Bi, Jie Xiong, Xue Han, Chao Yang, Xinghan Li, Guoqing Chen, Weihua Guo & Weidong Tian

  3. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China

    Fei Bi, Jie Xiong, Xue Han, Chao Yang, Xinghan Li, Guoqing Chen, Weihua Guo & Weidong Tian

  4. National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China

    Fei Bi, Xue Han, Chao Yang, Xinghan Li, Guoqing Chen, Weihua Guo & Weidong Tian

  5. Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, South Peoples Road, Chengdu, 610041, China

    Fei Bi, Xue Han & Weihua Guo

  6. Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China

    Jie Xiong, Xinghan Li & Weidong Tian

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  1. Fei Bi
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Contributions

BF, experiments performing, data collection and analyzing and manuscript drafting; XJ, HX and YC, experiments interpretation and data analyzing; LXH and CGQ, data analyzing; TWD and GWH, conception and design, supervision of project conduction; BF and GWH, critical revision of the manuscript. The authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Weihua Guo or Weidong Tian.

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Conflict of interest

The authors have no financial, personal, or other conflicts of interest to disclose. We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of this manuscript.

Ethics approval and consent to participate

Ethical approval to report this case was obtained from Ethics Committee of the State Key Laboratory of Oral Diseases, West China Hospital of Stomatology (WCHSIRB-D-2012-058). All animal experiments were conducted in accordance with the principles and procedures of the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals and approved by the Ethics Committee of the State Key Laboratory of Oral Diseases, West China Hospital of Stomatology (Chengdu, Sichuan).

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Bi, F., Xiong, J., Han, X. et al. Dental follicle cells show potential for treating Parkinson’s disease through dopaminergic-neuronogenic differentiation. Human Cell 35, 1708–1721 (2022). https://doi.org/10.1007/s13577-022-00774-6

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