Using stem cells, scientists have managed to restore nerve function in monkeys with Parkinson’s disease. The findings may change therapeutic practices in humans.
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iPSCs are cells that have been taken from a child or an adult’s tissue and genetically modified to resemble embryonic stem cells – that is, to be able to take the form of any other adult cell types.
In the case of Parkinson’s, scientists have been
These brain cells are the primary source of dopamine – the neurotransmitter that helps to regulate voluntary movement, mood, stress, and reward, among other things.
Previously, researchers have been able to restore motor function in rats and primates with Parkinson’s-like symptoms by implanting dopaminergic neurons derived from human iPSCs. But until now, no studies have investigated the long-term impact of such a practice in primates.
In this context, a team of researchers led by Jun Takahashi, of the Center for iPS Cell Research and Application at the Kyoto University in Japan, set out to implant these neurons in the brains of long-tailed macaques and evaluate the safety and functionality of such a practice over time.
Takahashi and colleagues transplanted cells from both healthy human adults and adults with Parkinson’s into the primates’ brains. To simulate Parkinson’s disease in the primates, the researchers treated them with
The scientists used a neurological rating scale to assess the neurological effect of the transplant, as well as video recordings to analyze the primates’ spontaneous movements.
Additionally, to evaluate the “survival, expansion, and function” of the transplanted neurons and the immune response from the primates’ brain, the researchers used magnetic resonance imaging (MRI) and positron emission tomography (PET).
To assess the safety of the procedure, the researchers clinically followed the primates for 2 years.
Cell analyses revealed that the dopaminergic neurons, when they reached maturity, extended their axons and dendrites into the striatum of the host.
The researchers found that “human [iPSC-]derived dopaminergic progenitor cells survived and functioned as midbrain dopaminergic neurons, [increasing] spontaneous movement of the monkeys after transplantation.”
Additionally, over a period of 2 years, Takahashi and team did not find any cell-derived tumors in the brain of the primates, nor did they register any strong immune response to the transplant.
In another article published in the journal Nature Communications, the authors show how the immune response can be improved even further.
By matching a group of proteins called major histocompatibility complex proteins (MHCs) of the iPSCs to the MHC of the host, the neuron survival is improved, and the immune response against the neurons is reduced, write the researchers.
Overall, the findings suggest that, although more research is needed, such translational techniques could soon be used to treat human patients. The authors conclude:
“This preclinical study using a primate model indicates that human iPS cell-derived dopaminergic progenitors are clinically applicable for the treatment of patients with PD.”