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Research conducted by scientists has revealed that the combination of stem cells and T-cells, which are referred to as Tregs and help curb extreme reactions in the immune system, can increase the survival rate of neurons in the brains of rodent models of Parkinson’s disease and even reduce the motor symptoms associated with the disorder.

A new strategy to improve clinical outcomes for stem cell-based therapies for Parkinson’s in humans is suggested by these findings. Such therapies strive to replace the dopamine-producing nerve cells that are lost in people with the neurodegenerative disorder.

“We have now made a major breakthrough using immune cells to improve delivery, survival, and recovery for neuronal cell therapies. Our findings show the power and flexibility of cell therapy to be modified and enhanced to become a realistic modality to treat conditions like Parkinson’s,” Dr. Kwang-Soo Kim, the lead author of the study and a researcher at the molecular neurobiology laboratory at McLean Hospital in Massachusetts, stated in a press release.

The gradual decline of dopaminergic nerve cells, which are responsible for producing dopamine, in a specific area of the midbrain known as the substantia nigra is the hallmark of Parkinson’s disease. Dopamine is a neurotransmitter that performs an essential function in the brain.

Levodopa is an existing treatment used to replenish depleted dopamine levels; however, it only provides temporary relief from symptoms such as tremors or stiffness. Over time, the effectiveness of this and similar treatments tends to decline.

Researchers are actively working on plans to create alternative sources for dopamine-producing neurons that have been lost, employing cell-based treatments. Two of the primary methods which are being utilized are midbrain dopaminergic neurons created from stem cells such as iPSCs, which are made from an individual’s own cells, as well as embryonic stem cells. These two types of cells possess the potential to create almost any kind of cell in a human body.

Despite the intentions of cell-based therapies to resolve the disease’s underlying cause, results have yet to be seen, due to dopaminergic neurons being incapable of implanting and persisting. In order for advances to be made, it is essential to comprehend the brain’s reaction to the transplanted cells, particularly the reactions of the immune cells present.

The McLean and Massachusetts General Hospital scientists used rodent models to progress their research initiative. In particular, they transplanted midbrain dopamine progenitor cells (mDAPs) from a Parkinson’s patient’s induced pluripotent stem cells (iPSCs) into the brains of the rodents. These dopamine progenitor cells are a type of stem cell that can turn into dopamine-producing neurons and can play a pivotal role in growing and replenishing dopamine neurons in the brain.

Previous research conducted by the team uncovered an inflammatory reaction in the brain – labelled “needle-trauma” – that was initiated by the brain surgery and involved the penetration of immune cells. Upon examination of the brain tissue two weeks post-transplant, it was revealed that a mere 10% of mDAPs cells had managed to survive the procedure. This same result was sustained when the team conducted transplants with two other sources.

The researchers speculated that the inflammatory response observed may be the cause of the rapid death of the transplanted cells. To explore this possibility, they hypothesized that co-transplanting regulatory T cells (also known as Tregs) along with the mDAPs could potentially reduce the acute neuroinflammation. Tregs are a type of immune cell which work to maintain a balanced immune system by controlling excessive immune responses.

By transferring both cell types, a positive side effect was seen: the growth of cells not containing dopamine, such as inflammatory cells, was prevented.

“This finding is very significant because a potential hazard associated with cell transplantation is often the outgrowth of undesirable, potentially harmful cells,” Kim said. “The most important criterion for cell therapy is safety.”

The implications of these results are important for other diseases affecting the nervous system that might take advantage of these cell-based treatments.

“Needle trauma is a universal issue in cell therapies in the nervous system, not just for dopaminergic neurons or Parkinson’s disease,” said, Bob Carter, MD, PhD, chief of neurosurgery at Mass General and one of the study’s authors, spoke of the findings.

“Our principles can be applied widely to any cell therapy for other (neuro)degenerative disorders such as Alzheimer’s, ALS [amyotrophic lateral sclerosis], or Huntington’s,” Carter said.

Kim suggests that further research is necessary in order to fully ascertain the wellbeing of patients through co-transplantation of Tregs and to discover the ways in which Tregs promote the persistence of neurons that produce dopamine. However, at present, this study is restricted by its usage of rodents as models.

The results of this research indicate that the co-transplantation system outlined is effective. “Effectively reduces the needle trauma induced death of mDANs, providing a potential strategy to achieve better clinical outcomes for cell therapy in Parkinson’s disease,” the researchers worte.

The Mass General Brigham launched its Gene and Cell Therapy Institute in order to bring scientific discoveries closer to human clinical trials and, ultimately, translate them into life-changing treatments for patients.

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