Immature Midbrain Dopaminergic Neurons Derived from Floor‐Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease

Immature Midbrain Dopaminergic Neurons Derived from Floor‐Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease
Title:
Immature Midbrain Dopaminergic Neurons Derived from Floor‐Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease
Other Titles:
Stem Cells Translational Medicine
Keywords:
Publication Date:
26 June 2017
Citation:
Qiu, L., Liao, M.‐C., Chen, A.K., Wei, S., Xie, S., Reuveny, S., Zhou, Z.D., Hunziker, W., Tan, E.K., Oh, S.K.W. and Zeng, L. (2017), Immature Midbrain Dopaminergic Neurons Derived from Floor‐Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease. STEM CELLS Translational Medicine, 6: 1803-1814. doi:10.1002/sctm.16-0470
Abstract:
Recent reports have indicated human embryonic stem cells‐derived midbrain dopamine (mDA) neurons as proper cell resources for use in Parkinson's disease (PD) therapy. Nevertheless, no detailed and systematic study has been conducted to identify which differentiation stages of mDA cells are most suitable for transplantation in PD therapy. Here, we transplanted three types of mDA cells, DA progenitors (differentiated in vitro for 16 days [D16]), immature DA neurons (D25), and DA neurons (D35), into PD mice and found that all three types of cells showed high viability and strong neuronal differentiation in vivo. Both D25 and D35 cells showed neuronal maturation and differentiation toward TH+ cells and, accordingly, satisfactory behavioral functional recovery. However, transplanted D16 cells were less capable of producing functional recovery. These findings provide a valuable guideline for standardizing the differentiation stage of the transplantable cells used in clinical cell therapy for PD. Stem Cells Translational Medicine 2017;6:1803–1814. Significance Statement Cell replacement is considered the promising treatment for Parkinson's disease (PD). Nevertheless, no detailed and systematic study has been conducted to identify which differentiation stages of mDA cells are most suitable for transplantation in PD therapy. The present study showed that the immature mDA neurons were with the best TH+ differentiation and able to recover rotation behavior in PD mice. In contrast, mDA progenitors showed discouraging TH+ differentiation and no behavioral recovery.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
We thank Dr. Wei Zhang and Ms. Yu Ming Lim for technical support. This research was supported by the Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council. We also acknowledge the Agency for Science Technology and Research (A*STAR) for generous funding of this research. E.K.T.: Honoraria as an editor for European Journal of Neurology and Parkinsonism & Related Disorders Research funding from the National Medical Research Council. The other authors indicated no potential conflicts of interest.
Description:
ISSN:
2157-6564
2157-6580
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