Finding may lead to transplanting dopamine neurons taken from stem cells grown in labs
Harvard Stem Cell Institute researchers at McLean Hospital have found that fetal dopamine cells transplanted into the brains of patients with Parkinson’s disease were able to remain healthy and functional for up to 14 years, a finding that could lead to new and better therapies for the illness.
The discovery, reported in the June 5, 2014 issue of the journal Cell Reports, could pave the way for researchers to begin transplanting dopamine neurons taken from stem cells grown in laboratories, a way to get treatments to many more patients in an easier fashion.
“We have shown in this paper that the transplanted cells connect and live well and do all the required functions of nerve cells for a very long time,” said Ole Isacson, MD, director of the Neuroregeneration Research Institute at McLean and a Principal Faculty member of the Harvard Stem Cell Institute.
The researchers looked at the brains of five patients who got fetal cell transplants over a period of 14 years and found that their dopamine transporters (DAT), proteins that pump the neurotransmitter dopamine, and mitochondria, the power plants of cells, were still healthy at the time the patients died, in each case of causes other than Parkinson’s.
The fact that these cells had remained healthy indicated that the transplants had been successful and that the transplanted cells had not been corrupted as some researchers had suggested they likely had been in other studies, said Isacson, lead author of the paper.
“These findings are critically important for the rational development of stem cell-based dopamine neuronal replacement therapies for Parkinson’s,” the paper concluded.
So far, about 25 patients worldwide have been treated with this particular method of transplanting fetal dopamine cells over a period of two decades and most saw their symptoms improve markedly, he said.
Fetal cell transplants can reduce both Parkinson’s symptoms for many years and can reduce the need for dopamine replacement drugs, even though they can take months or years to start working, the paper said.
However, Isacson, also a professor of neurology and neuroscience at Harvard Medical School, said proof had been lacking that the transplanted cells were able to remain healthy -- until this study. This is important for research in the transplant field to move ahead, he said.
All of the patients were in the late stages of Parkinson’s disease at the time of their transplants. Parkinson’s is a disease characterized by tremors, rigidity, slowness of movement and poor balance. It is a chronic, progressive disease that results when dopamine-producing nerve cells in a part of the brain die or are impaired.
Isacson said there was a need to understand how transplanted neurons could survive despite ongoing disease process in the patients’ brains. He said there has been controversy among scientists, some of whom believe that the transplanted cells could be corrupted by toxic proteins associated with the disease process, even at the same time patients seemed to be doing better.
“Everything we saw looked very healthy,” he said, referring to the dopamine transporters and mitochondria cells.
He said the method used to transplant the cells into these patients’ brains was different than another method used on about 60 other patients worldwide. In some of those other trials, scientists said the cells might have been damaged as a result of the disease process.
It may have been that the method used on the patients in this study, which injected tiny bits of liquefied dopamine nerve cells into the brain via a thin needle, was superior to the method used in other studies, which transplanted larger chunks of nerve cells using a larger needle, he said. The transplants on the patients in this study were done in Canada.
In this study, the researchers led by Isacson compared the patients’ own dopamine producing cells with the transplanted ones. “We found very different patterns,” he said.
The difference was seen in the DAT and mitochondria, which were unhealthy around the patients’ own dopamine neurons and healthy around the transplanted ones. “The transplanted cells don’t have the disease,” he said.
“This is very important in the quest for new therapies,” he added.
It is very difficult to obtain dopamine nerve cells from fetal tissue, he said. It would be far easier to grow the cells in a laboratory from stem cells, he noted. There have been no stem cell transplants as of yet for Parkinson’s patients.
Co-authors included Penelope J. Hallett, of Harvard University and the McLean NRI; and Oliver Cooper, Damaso Sadi, Harold Robinson and Ivar Mendez, all of Dalhousie University and the Queen Elizabeth II Health Sciences Centre, Halifax, Canada.
The study was funded by the Harvard Stem Cell Institute, the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Canadian Institute of Health Research, Queen Elizabeth II Health Sciences Centre, the Consolidated Anti-Aging Foundation, the Poul Hansen Family and the Harold and Ronna Cooper Family.
Cited: Hallett et al., Long-Term Health of Dopaminergic Neuron Transplants in Parkinson’s Disease Patients, Cell Reports (June 5, 2014), http://dx.doi.org/10.1016/j.celrep.2014.05.027
Story provided by Jenna Brown/McClean Hospital.