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Int. J. Mol. Sci. 2018, 19(3), 720; https://doi.org/10.3390/ijms19030720

Effects of Passage Number and Differentiation Protocol on the Generation of Dopaminergic Neurons from Rat Bone Marrow-Derived Mesenchymal Stem Cells

1
Field Neurosciences Institute Laboratory for Restorative Neuroscience, Central Michigan University, Mount Pleasant, MI 48859, USA
2
Neuroscience Program, Central Michigan University, Mount Pleasant, MI 48859, USA
3
College of Humanities and Social and Behavioral Sciences, Psychology Department, Central Michigan University, Mount Pleasant, MI 48859, USA
4
College of Medicine, Central Michigan University, Mount Pleasant, MI 48859 USA
5
Field Neurosciences Institute, 4677 Towne Centre Rd. Suite 101, Saginaw, MI 48604, USA
These authors contribute equally to the work.
*
Author to whom correspondence should be addressed.
Received: 9 January 2018 / Revised: 9 February 2018 / Accepted: 28 February 2018 / Published: 2 March 2018
(This article belongs to the Section Biochemistry)
Full-Text   |   PDF [7399 KB, uploaded 2 March 2018]   |  

Abstract

Multiple studies have demonstrated the ability of mesenchymal stem cells (MSCs) to differentiate into dopamine-producing cells, in vitro and in vivo, indicating their potential to be used in the treatment of Parkinson’s disease (PD). However, there are discrepancies among studies regarding the optimal time (i.e., passage number) and method for dopaminergic induction, in vitro. In the current study, we compared the ability of early (P4) and later (P40) passaged bone marrow-derived MSCs to differentiate into dopaminergic neurons using two growth-factor-based approaches. A direct dopaminergic induction (DDI) was used to directly convert MSCs into dopaminergic neurons, and an indirect dopaminergic induction (IDI) was used to direct MSCs toward a neuronal lineage prior to terminal dopaminergic differentiation. Results indicate that both early and later passaged MSCs exhibited positive expression of neuronal and dopaminergic markers following either the DDI or IDI protocols. Additionally, both early and later passaged MSCs released dopamine and exhibited spontaneous neuronal activity following either the DDI or IDI. Still, P4 MSCs exhibited significantly higher spiking and bursting frequencies as compared to P40 MSCs. Findings from this study provide evidence that early passaged MSCs, which have undergone the DDI, are more efficient at generating dopaminergic-like cells in vitro, as compared to later passaged MSCs or MSCs that have undergone the IDI. View Full-Text
Keywords: Parkinson’s disease; mesenchymal stem cells; dopaminergic neurons; passaging; induction protocol Parkinson’s disease; mesenchymal stem cells; dopaminergic neurons; passaging; induction protocol
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Shall, G.; Menosky, M.; Decker, S.; Nethala, P.; Welchko, R.; Leveque, X.; Lu, M.; Sandstrom, M.; Hochgeschwender, U.; Rossignol, J.; Dunbar, G. Effects of Passage Number and Differentiation Protocol on the Generation of Dopaminergic Neurons from Rat Bone Marrow-Derived Mesenchymal Stem Cells. Int. J. Mol. Sci. 2018, 19, 720.

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