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Open Access 01-12-2018 | Research article

Altered development of dopaminergic neurons differentiated from stem cells from human exfoliated deciduous teeth of a patient with Down syndrome

Authors: Thanh Thi Mai Pham, Hiroki Kato, Haruyoshi Yamaza, Keiji Masuda, Yuta Hirofuji, Hiroshi Sato, Huong Thi Nguyen Nguyen, Xu Han, Yu Zhang, Tomoaki Taguchi, Kazuaki Nonaka

Published in: BMC Neurology | Issue 1/2018

Abstract

Background

Down syndrome (DS) is a common developmental disorder resulting from the presence of an additional copy of chromosome 21. Abnormalities in dopamine signaling are suggested to be involved in cognitive dysfunction, one of the symptoms of DS, but the pathophysiological mechanism has not been fully elucidated at the cellular level. Stem cells from human exfoliated deciduous teeth (SHED) can be prepared from the dental pulp of primary teeth. Importantly, SHED can be collected noninvasively, have multipotency, and differentiate into dopaminergic neurons (DN). Therefore, we examined dopamine signaling in DS at the cellular level by isolating SHED from a patient with DS, differentiating the cells into DN, and examining development and function of DN.

Methods

Here, SHED were prepared from a normal participant (Ctrl-SHED) and a patient with DS (DS-SHED). Initial experiments were performed to confirm the morphological, chromosomal, and stem cell characteristics of both SHED populations. Next, Ctrl-SHED and DS-SHED were differentiated into DN and morphological analysis of DN was examined by immunostaining. Functional analysis of DN was performed by measuring extracellular dopamine levels under basal and glutamate-stimulated conditions. In addition, expression of molecules involved in dopamine homeostasis was examined by quantitative real-time polymerase chain reaction and immunostaining. Statistical analysis was performed using two-tailed Student’s t-tests.

Results

Compared with Ctrl-SHED, DS-SHED showed decreased expression of nestin, a neural stem-cell marker. Further, DS-SHED differentiated into DN (DS-DN) exhibiting decreased neurite outgrowth and branching compared with Ctrl-DN. In addition, DS-DN dopamine secretion was lower than Ctrl-DN dopamine secretion. Moreover, aberrant expression of molecules involved in dopaminergic homeostasis was observed in DS-DN.

Conclusions

Our results suggest that there was developmental abnormality and DN malfunction in the DS-SHED donor in this study. In the future, to clarify the detailed mechanism of dopamine-signal abnormality due to DN developmental and functional abnormalities in DS, it is necessary to increase the number of patients for analysis. Non-invasively harvested SHED may be very useful in the analysis of DS pathology.

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Title: Altered development of dopaminergic neurons differentiated from stem cells from human exfoliated deciduous teeth of a patient with Down syndrome
Authors: Thanh Thi Mai Pham
Hiroki Kato
Haruyoshi Yamaza
Keiji Masuda
Yuta Hirofuji
Hiroshi Sato
Huong Thi Nguyen Nguyen
Xu Han
Yu Zhang
Tomoaki Taguchi
Kazuaki Nonaka
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Neurology / Issue 1/2018
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-018-1140-2

At a glance: The STEP trials

Springer Medicine

Altered development of dopaminergic neurons differentiated from stem cells from human exfoliated deciduous teeth of a patient with Down syndrome

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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