One of the last steps before treating patients with an experimental brain cell therapy is confirming that the therapy works in monkeys. Now, a team of scientists from the Center for Research and Application of iPS Cells (Induced Pluripotent Stem Cells) at the University of Kyoto (Japan) has succeeded in helping monkeys with symptoms of Parkinson’s disease show significant improvement two years after being transplanted. neurons prepared from human iPS cells. The study will lead to the first iPS cell-based therapy for neurodegenerative diseases in humans.
Parkinson’s disease degenerates a specific type of cell in the brain known as dopaminergic neurons (DA), because when symptoms are first detected, the patient has already lost more than half of their DA neurons.
Several studies have shown that transplantation of dopamine neurons – those brain cells that are responsible for producing dopamine and transmitting it to other cells of the nervous system – made from fetal cells can mitigate the disease. However, the use of fetal tissues is controversial.
“ Our research has shown that DA neurons made from iPS cells are as good as DA neurons made from the fetal midbrain , because iPS cells are easy to obtain, we can standardize them to use only the best iPS cells for therapy.” the authors explain to the journal Nature.
To test the safety and efficacy of DA neurons made from human iPS cells, Tetsuhiro Kikuchi, one of the researchers, transplanted the cells into the brains of monkeys.
“We made DA neurons from different iPS cell lines, some were made with iPS cells from healthy donors, others were made from Parkinson’s disease patients,” says Kikuchi,
It is generally assumed that the outcome of a cell therapy depends on the number of transplanted cells that survive, but Kikuchi found that this was not the case. Before the number of cells, the important thing here was their quality . “The quality of the donor cells had a great effect on the survival of the DA neuron,” Kikuchi said.
To understand why, the experts looked for genes that show different levels of expression, finding 11 genes that could mark the quality of the parents. One of those genes was Dlk1.
To evaluate cell survival in the host brain, magnetic resonance imaging (MRI) and electronic positional tomography (PET) were suitable options for evaluating the patient after surgery, which can be very useful for clinical trials since they are non-invasive techniques.
Scientists hope to begin recruiting patients for this iPS cell-based therapy before the end of next year. “This study is our response to bring iPS cells into clinical settings,” Takahashi clarified. They found no tumors or signs of disease in these cells, so the treatment has proven to be safe.
The findings suggest that this treatment will improve outcomes in patients with neurodegenerative diseases.
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Referencia: Tetsuhiro Kikuchi, Asuka Morizane, Daisuke Doi, Hiroaki Magotani, Hirotaka Onoe, Takuya Hayashi, Hiroshi Mizuma, Sayuki Takara, Ryosuke Takahashi, Haruhisa Inoue, Satoshi Morita, Michio Yamamoto, Keisuke Okita, Masato Nakagawa, Malin Parmar, Jun Takahashi. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature, 2017; 548 (7669): 592 DOI: 10.1038 / nature23664
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