AUG 31, 2017 6:57 PM PDT

Stem Cell-based Therapy Alleviated Parkinson's in Monkeys

WRITTEN BY: Carmen Leitch

The development of clinical treatments usually takes many years. After laboratory research is done, monkeys are often used in the final stages before human testing. One such experiment has shown success; neurons made from human stem cells were transplanted into monkeys, and the animals showed significant improvement. This work has demonstrated that it may be possible to treat human neurodegenerative diseases with this therapy.

Reported in Nature, this work was performed by researchers at the Center for iPS Cell Research and Application (CiRA), Kyoto University, Japan and is outlined in the video.

In Parkinson’s disease, a type of nerve cell in the brain called a dopaminergic (DA) neuron is slowly destroyed. However, by the time the disease is diagnosed because a person is showing symptoms, it’s estimated that half of the DA neurons have already been lost. Previous work has shown that transplanting DA neurons from cells at the fetal stage can alleviate the disorder. Fetal tissue remains a highly controversial issue though and has led researchers to seek other ways to generate these important neurons.

A breakthrough has allowed stem cells to be created from skin or blood cells; the newly created stem cells are called induced pluripotent stem (iPS) cells. Lead author of the work and neurosurgeon Professor Takahashi wanted to make DA neurons from such iPS cells. "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,” Takahashi said.

Monkeys were used to check the safety and efficacy of using DA neurons generated from iPS cells. Neurosurgeon Tetsuhiro Kikuchi, who works in the Takahashi lab, transplanted these cells into the monkeys’ brains.

"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," explained Kikuchi. He noted that the method that converts iPS cells into neurons is ready for use in clinical trials.

It has been assumed that an effective stem cell therapy is dependent on the number of transplanted cells that survive. Kikuchi found, however, that stem cell quality was more important than how many last.

"Each animal received cells prepared from a different iPS cell donor. We found the quality of donor cells had a large effect on the DA neuron survival," noted Kikuchi.

The investigators wanted to know why this was happening and searched for genes that were differentially expressed in the cells. Eleven genes were identified as biomarkers for progenitor cell quality; one was the Dlk1 gene.

"Dlk1 is one of the predictive markers of cell quality for DA neurons made from embryonic stem cells and transplanted into [a] rat. We found Dlk1 in DA neurons transplanted into [a] monkey. We are investigating Dlk1 to evaluate the quality of the cells for clinical applications."

This research also showed that patients could be evaluated after this surgery with simple tools - position electron tomography (PET) and magnetic resonance imaging (MRI).

Crab-eating macaque (Macaca fascicularis), portrait, Singapore / Credit: Eigene Aufnahme von André Ueberbach/Own production Author:André Ueberbach

"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.

The investigators are trying to start recruiting patients for this therapy sometime next year. "This study is our answer to bring iPS cells to clinical settings," concluded Takahashi.

 

Sources: Science Daily via CiRA, Nature

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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