AsianScientist (Sep. 11, 2017) – Scientists in Japan have demonstrated that human induced pluripotent stem (iPS) cells could one day be used to treat Parkinson’s disease. They published their findings in the journal Nature.
Parkinson’s disease degenerates a specific type of cells in the brain known as dopaminergic (DA) neurons. It has been reported that when symptoms are first detected, a patient will have already lost more than half of his or her DA neurons. Several studies have revealed that the transplantation of DA neurons made from fetal cells can mitigate the disease. However, the use of fetal tissues is controversial. On the other hand, iPS cells can be made from blood or skin, providing a potentially inexhaustible source of stem cells for regenerative therapy.
In this study, a team of researchers led by Professor Jun Takahashi of Kyoto University converted iPS cells into DA neurons for use in regenerative therapy.
“Our research has shown that DA neurons made from iPS cells are just as good as DA neurons made from fetal midbrain. Because iPS cells are easy to obtain, we can standardize them to only use the best iPS cells for therapy,” he said.
To test the safety and effectiveness of DA neurons made from human iPS cells, Dr. Tetsuhiro Kikuchi, a neurosurgeon working in the Takahashi lab, transplanted the cells into the brains of monkeys.
“We made DA neurons from different iPS cells lines. Some were made with iPS cells from healthy donors. Others were made from Parkinson’s disease patients,” said Kikuchi, who added that the differentiation method used to convert iPS cells into neurons is suitable for clinical trials.
It is generally assumed that the outcome of a cell therapy will depend on the number of transplanted cells that survive, but Kikuchi found this was not the case. More important than the number of cells was the quality of the cells.
“Each animal received cells prepared from a different iPS cell donor. We found that the quality of donor cells had a large effect on the DA neuron survival,” Kikuchi said.
To understand why, he looked for genes that showed different expression levels, finding 11 genes that could mark the quality of the progenitors. One of those genes was Dlk1.
“Dlk1 is one of the predictive markers of cell quality for DA neurons made from embryonic stem cells and transplanted into rat. We found Dlk1 in DA neurons transplanted into monkey. We are investigating Dlk1 to evaluate the quality of the cells for clinical applications.”
Another feature of the study that is expected to extend to clinical study is the method used to evaluate cell survival in the host brains. The study demonstrated that magnetic resonance imaging (MRI) and position electron tomography (PET) are options for evaluating the patient’s progress post-surgery.
“MRI and PET are non-invasive imaging modalities. Following cell transplantation, we must regularly observe the patient. A non-invasive method is preferred,” said Takahashi.
Notably, the researchers report that monkeys with Parkinson’s disease symptoms show significant improvement over two years after being transplanted with neurons prepared from human iPS cells. The group is hopeful that it can begin recruiting patients for this iPS cell-based therapy before the end of next year.
The article can be found at: Kikuchi et al. (2017) Human iPS Cell-derived Dopaminergic Neurons Function in a Primate Parkinson’s Disease Model.
Source: Kyoto University; Photo: Misaki Ouchida/CiRA.
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