Abstract
Background
This study explored the neural differentiation and therapeutic effects of stem cells
from human exfoliated deciduous teeth (SHED) in a rat model of Parkinson's disease
(PD).
Methods
The SHED were isolated from fresh dental pulp and were induced to differentiate to
neurons and dopamine neurons by inhibiting similar mothers against dpp (SMAD) signaling
with Noggin and increase conversion of dopamine neurons from SHED with CHIR99021,
Sonic Hedgehog (SHH) and FGF8 in vitro. The neural-primed SHED were transplanted to the striatum of 6-hydroxydopamine (6-OHDA)–induced
PD rats to evaluate their neural differentiation and functions in vivo.
Results
These SHED were efficiently differentiated to neurons (62.7%) and dopamine neurons
(42.3%) through a newly developed method. After transplantation, the neural-induced
SHED significantly improved recovery of the motor deficits of the PD rats. The grafted
SHED were differentiated into neurons (61%), including dopamine neurons (22.3%), and
integrated into the host rat brain by forming synaptic connections. Patch clamp analysis
showed that neurons derived from grafted SHED have the same membrane potential profile
as dopamine neurons, indicating these cells are dopamine neuron-like cells. The potential
molecular mechanism of SHED transplantation in alleviating motor deficits of the rats
is likely to be mediated by neuronal replacement and immune-modulation as we detected
the transplanted dopamine neurons and released immune cytokines from SHED.
Conclusion
Using neural-primed SHED to treat PD showed significant restorations of motor deficits
in 6-OHDA–induced rats. These observations provide further evidence that SHED can
be used for cell-based therapy of PD.
Key Words
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Article info
Publication history
Published online: March 22, 2018
Accepted:
February 21,
2018
Received:
October 30,
2017
Identification
Copyright
© 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
