Factors Derived from Human Exfoliated Deciduous Teeth Stem Cells Reverse Neurological Deficits in a Zebrafish Model of Parkinson's Disease

Overview

Journal J Dent Sci

Specialty Dentistry

Date 2024 Sep 30

PMID 39347052

Authors

Yong-Ren Chen

Chin-Chean Wong

Yi-No Chen

Bing-Heng Yang

Po-Hui Lee

Chia-Yang Shiau

Kuo-Chuan Wang

Chung-Hsing Li

Affiliations

Soon will be listed here.

Abstract

Background/purpose: Mesenchymal stem cells exhibit therapeutic efficacy for brain injury. This study examined the effect of mesenchymal stem cells derived from human exfoliated deciduous teeth (SHED) on alleviating symptoms of Parkinson's disease (PD).

Materials And Methods: SHED were isolated to examine the biosafety and bioavailability of stem cells derived from human exfoliated deciduous teeth-derived conditioned medium (SHED-CM) for the alleviation of PD symptoms in a 6-hydroxydopamine (6-OHDA)-induced PD zebrafish model.

Results: SHED-CM administration did not induce neurological, skin or muscle toxicity in control zebrafish at any dose, and estrogen equivalent testing showed no chronic toxicants. Induction of PD with 6-OHDA suppressed zebra SHED-CM was administered to zebrafish treated with 6-OHDA to induce PD symptoms. Similar to nomifensine, a drug with proven anti-PD potential, SHED-CM repaired the motor deficiencies in the zebrafish PD model.

Conclusion: Our results indicate the biosafety of SHED-CM and its therapeutic potential in treating PD in a zebrafish model.

References

Shimojima C, Takeuchi H, Jin S, Parajuli B, Hattori H, Suzumura A . Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis. J Immunol. 2016; 196(10):4164-71. DOI: 10.4049/jimmunol.1501457. View

Vaz R, Outeiro T, Ferreira J . Zebrafish as an Animal Model for Drug Discovery in Parkinson's Disease and Other Movement Disorders: A Systematic Review. Front Neurol. 2018; 9:347. PMC: 5992294. DOI: 10.3389/fneur.2018.00347. View

Vaughan R, Foster J . Mechanisms of dopamine transporter regulation in normal and disease states. Trends Pharmacol Sci. 2013; 34(9):489-96. PMC: 3831354. DOI: 10.1016/j.tips.2013.07.005. View

Langston J . Parkinson's disease: current and future challenges. Neurotoxicology. 2002; 23(4-5):443-50. DOI: 10.1016/s0161-813x(02)00098-0. View

Sanchez-Guajardo V, Barnum C, Tansey M, Romero-Ramos M . Neuroimmunological processes in Parkinson's disease and their relation to α-synuclein: microglia as the referee between neuronal processes and peripheral immunity. ASN Neuro. 2013; 5(2):113-39. PMC: 3639751. DOI: 10.1042/AN20120066. View

Chen Y, Lai P, Chien Y, Lee P, Lai Y, Ma H . Improvement of Impaired Motor Functions by Human Dental Exfoliated Deciduous Teeth Stem Cell-Derived Factors in a Rat Model of Parkinson's Disease. Int J Mol Sci. 2020; 21(11). PMC: 7312764. DOI: 10.3390/ijms21113807. View

Zheng W, Kar S, Dore S, Quirion R . Insulin-like growth factor-1 (IGF-1): a neuroprotective trophic factor acting via the Akt kinase pathway. J Neural Transm Suppl. 2001; (60):261-72. DOI: 10.1007/978-3-7091-6301-6_17. View

Parng C, Roy N, Ton C, Lin Y, McGrath P . Neurotoxicity assessment using zebrafish. J Pharmacol Toxicol Methods. 2006; 55(1):103-12. DOI: 10.1016/j.vascn.2006.04.004. View

Chen X, Xu S, Tan T, Lee S, Cheng S, Lee F . Toxicity and estrogenic endocrine disrupting activity of phthalates and their mixtures. Int J Environ Res Public Health. 2014; 11(3):3156-68. PMC: 3987027. DOI: 10.3390/ijerph110303156. View

10.

Sui Y, Bullock K, Erickson M, Zhang J, Banks W . Alpha synuclein is transported into and out of the brain by the blood-brain barrier. Peptides. 2014; 62:197-202. PMC: 4378645. DOI: 10.1016/j.peptides.2014.09.018. View

11.

Castellano J, Mosher K, Abbey R, McBride A, James M, Berdnik D . Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature. 2017; 544(7651):488-492. PMC: 5586222. DOI: 10.1038/nature22067. View

12.

Mir S, Cai W, Carlson S, Saatman K, Andres D . IGF-1 mediated Neurogenesis Involves a Novel RIT1/Akt/Sox2 Cascade. Sci Rep. 2017; 7(1):3283. PMC: 5468318. DOI: 10.1038/s41598-017-03641-9. View

13.

Tenente I, Tang Q, Moore J, Langenau D . Normal and malignant muscle cell transplantation into immune compromised adult zebrafish. J Vis Exp. 2015; (94). PMC: 4354485. DOI: 10.3791/52597. View

14.

Anselmi L, Bove C, Coleman F, Le K, Subramanian M, Venkiteswaran K . Ingestion of subthreshold doses of environmental toxins induces ascending Parkinsonism in the rat. NPJ Parkinsons Dis. 2018; 4:30. PMC: 6160447. DOI: 10.1038/s41531-018-0066-0. View

15.

Hayashi Y, Kato H, Nonaka K, Nakanishi H . Stem cells from human exfoliated deciduous teeth attenuate mechanical allodynia in mice through distinct from the siglec-9/MCP-1-mediated tissue-repairing mechanism. Sci Rep. 2021; 11(1):20053. PMC: 8501097. DOI: 10.1038/s41598-021-99585-2. View

16.

Zhang N, Chen B, Wang W, Chen C, Kang J, Deng S . Isolation, characterization and multi-lineage differentiation of stem cells from human exfoliated deciduous teeth. Mol Med Rep. 2016; 14(1):95-102. PMC: 4918624. DOI: 10.3892/mmr.2016.5214. View

17.

Ueda T, Ito T, Inden M, Kurita H, Yamamoto A, Hozumi I . Stem Cells From Human Exfoliated Deciduous Teeth-Conditioned Medium (SHED-CM) is a Promising Treatment for Amyotrophic Lateral Sclerosis. Front Pharmacol. 2022; 13:805379. PMC: 8850386. DOI: 10.3389/fphar.2022.805379. View

18.

Rocha N, de Miranda A, Teixeira A . Insights into Neuroinflammation in Parkinson's Disease: From Biomarkers to Anti-Inflammatory Based Therapies. Biomed Res Int. 2015; 2015:628192. PMC: 4532803. DOI: 10.1155/2015/628192. View

19.

Chen Y, Wu Y, Mesri M, Chen C . Associations of Matrix Metalloproteinase-9 and Tissue Inhibitory Factor-1 Polymorphisms With Parkinson Disease in Taiwan. Medicine (Baltimore). 2016; 95(5):e2672. PMC: 4748918. DOI: 10.1097/MD.0000000000002672. View

20.

Miura M, Gronthos S, Zhao M, Lu B, Fisher L, Robey P . SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A. 2003; 100(10):5807-12. PMC: 156282. DOI: 10.1073/pnas.0937635100. View