Home | Breaking News | Parkinson’s disease: Production of dopamine neurons from stem cells steps closer
The new research should help refine stem cell engineering and transplanting methods prior to testing in clinical trials of Parkinson's disease.

Parkinson’s disease: Production of dopamine neurons from stem cells steps closer

WT24 Desk

Stem cell therapies for brain disorders like Parkinson’s disease are rapidly moving toward clinical trials,MNT reports. However, before such treatments can leave the lab, it is vitally important to be able to consistently produce high-quality stem cells for transplant into patients. Now, scientists in Sweden have identified some insights – plus a set of markers – that should help control the quality of stem cells engineered for clinical use in Parkinson’s disease.

The researchers – including teams from Lund University and the Karolinska Institute in Stockholm – report their work in two related studies published in the journal Cell Stem Cell.

In one study, the researchers take a closer look at the molecular pathways involved in the journey, from a stem cell to a dopamine neuron. In the other study, they discover some key features of dopamine cell development and what makes these cells different from other similar and neighboring neurons.

The findings should help fine-tune stem cell engineering to produce pure populations of high-quality dopamine neurons, they note.

Parkinson’s disease is a progressive brainwasting condition that affects movement. The symptoms include: tremors in the hands, limbs, jaw, and face; muscle rigidity; impaired posture, balance, and gait; and speech problems.

The disease primarily affects dopamine-producing brain cells or neurons in a part of the brain called the substantia nigra. As the disease progresses, these vital cells malfunction and die, leading to lower levels of dopamine, a chemical messenger essential for controlling movement.

The need to refine stem cell engineering

As the brain’s population of dopamine cells dwindle, they are not replaced. One great hope is that stem cell engineering may offer a way to transplant a pool of progenitor cells into the brains of patients so they make new supplies of dopamine cells.

In fact, one of the teams behind the new studies thought they had got very close to such a solution. In a breakthrough study published in 2014, they showed how it is possible to make dopamine cells from embryonic stem cells and transplant them into the brains of rats with Parkinson’s disease, to replace the lost cells.

Malin Parmar, professor in the faculty of medicine at Lund, led the earlier study and is also one of the leaders of the new research. She explains the unexpected delay that followed their high hopes from the first breakthrough:

“In our preclinical assessments of stem cell-derived dopamine neurons we noticed that the outcome in animal models varied dramatically, even though the cells were very similar at the time of transplantation. This has been frustrating and puzzling, and has significantly delayed the establishment of clinical cell production protocols.”

In one of the papers, the researchers discuss how a particular complication in the use of stem cells to treat brain diseases like Parkinson’s is that you cannot just produce a population of working dopamine cells in a dish and transplant them into the brain.

While some stem cell treatments – such as those undergoing trial for the treatment of macular degeneration – can use cells fully matured in the lab, in the case of brain diseases like Parkinson’s, you have to implant immature cells that only differentiate and mature after they are transplanted into the brain.

Animal models of Parkinson’s and other brain diseases show it can take months for the cells to mature and start working properly after transplant.

Ensuring quality of stem cells before transplant

The challenge is how to ensure that the cells are of the right quality before transplant, since it is going to be very difficult to keep an eye on their development once they are inside the brain.

In the first study, the researchers used modern global gene expression techniques and undertook experiments in over 30 batches of grafted human embryonic stem cell (hESC)-derived progenitors to look at predictive markers of high quality dopamine cell yield.

They found that many of the commonly used markers did not accurately predict the yield of the desired mature dopamine cells following transplants into live animal brains. Instead, they identified a specific set of markers that offer much higher predictive power.

“Using these markers, we developed a good manufacturing practice (GMP) differentiation protocol for highly efficient and reproducible production of transplantable dopamine progenitors from hESCs,” the authors note.

In the second study, the researchers undertook – using transcriptome-wide single-cell RNA sequencing techniques – a detailed investigation of how dopamine cells develop in the brains of mice. Among other things, they found a marker that can distinguish between developing dopamine cells and other similar neighboring cells. They suggest this should help refine current stem cell engineering methods to increase the proportion of desired dopamine precursor cells. The finding, they conclude, should “have important implications for cell replacement therapy” in Parkinson’s disease.

Leave a Reply

Your email address will not be published. Required fields are marked *


%d bloggers like this: