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Human Embryonic Stem Cells-derived Dopaminergic Neurons Alleviate Symptoms of Parkinson’s Disease in Monkeys
[ 2018-06-13 ]

Parkinson's disease (PD) is one of the leading neural degenerative disorders, which is primarily caused by death of dopaminergic neurons in substantia nigra. This type of disorder is now possibly treated using stem cell-based strategy, such as transplantation of human embryonic stem cells (hESCs) differentiated derivatives. However, prior to the clinical application of hESCs-derived cells, pre-clinical data was required to show their safety and efficacy.

Long term evaluation, especially in primates is in particular valuable for successful clinical transplantation.

Recently, a research team led by Prof. ZHOU Qi and Prof. HU Baoyang from the Institute for Stem Cell and Regeneration of Institute of Zoology, Chinese Academy of Sciences, published their data of a 2-year evaluation in PD monkeys on the safety and efficacy of dopaminergic neurons derived from parthenogenetic ESCs.

The research was published online in Stem Cell Reports.

In this study, they first generated PD monkey models by neurotoxin infusion. At the same time, dopaminergic neurons were produced under cGMP conditions using clinical grade hESCs. After undergoing strict quality tests, these cells were transplanted into brains of drug-induced PD monkeys.

After 9 months, some of the monkeys were euthanized for biopsy. The researchers used imaging methods combined with immunohistochemical analysis and blood biochemical tests to demonstrate that the implanted cells did not exhibit excessive proliferation or tumor formation.

Further study showed that the implanted cells can survive for a long term and further matured in vivo. And there was no immune rejection or other serious adverse events.

In addition, the grafts produced variable but apparent behavioral improvement for at least 24 months in most monkeys, indicating that clinical-grade hESCs can serve as a reliable source of cells for PD treatment. Their findings provided strong preclinical support for China’s first ESCs-based Phase I/IIa clinical study on PD.

This work was supported in part by grants from Ministry of Science and Technology, the National Natural Science Foundation of China, and the Key Research Projects of the Frontier Science of the Chinese Academy of Sciences.

Clinical-grade human parthenogenetic ESCs were differentiated into midbrain dopaminergic neurons under cGMP conditions using “embryoid body” and “floor plate” protocols. After passing strict quality tests, these cells were transplanted into brains of drug-induced PD monkeys for preclinical assessment.

 

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