Allogeneic MSCs in the Treatment of Parkinson's Disease

Parkinson's treatment has ushered in a new opportunity! Now, a research team from South Korea uses human fetal midbrain-derived dopamine neuron precursor cells to treat Parkinson's disease. After 10 years of follow-up, it has been proved that the therapy is safe and effective, bringing new opportunities for the treatment of Parkinson's disease.

Previous attempts were to use autologous or allogeneic pluripotent stem cells to differentiate into brain-specific cells and then transplant them to Parkinson's patients. Now, scientists use allogeneic fetal mesenchymal stem cells to directly derive more brain-specific cells to achieve more effective applications.

This new attempt is the first in the world! If it can be successful, it will not only save the time for laboratory cell preparation, but also bring opportunities for large-scale standardized production of brain-specific cells for wider clinical application.

This prospective, phase I/IIa, dose-escalation, open-label study (NCT01860794) enrolled 15 Parkinson's patients under the age of 70 and conducted a 10-year long-term follow-up. The results showed good efficacy and no side effects, immune rejection, inflammation and tumor formation.

This study proves that human fetal midbrain-derived dopamine neuron precursor cells are good candidates for Parkinson's stem cell therapy, which opens a new chapter for Parkinson's cell therapy and is expected to bring new opportunities for Parkinson's patients.

Parkinson's disease "new hope"

Parkinson's disease (Parkinson's disease, PD) is a slowly occurring neurodegenerative disease in the elderly with selective loss of dopamine (DA) neurons in the substantia nigra of the midbrain and a significant decrease in DA content in the striatum .

Due to the loss of neurons that control motor ability, Parkinson's patients will experience various motor dysfunctions. Tremors, slow movements, and muscle stiffness are common symptoms.

Based on the principle of "make up what is lacking" , traditional clinical treatment focuses on supplementing drugs such as dopamine receptor agonists and enhancers to delay the development of Parkinson's. But over time, drugs can also have off-target effects, gradually lose efficacy and even produce side effects, including neurological symptoms and movement disorders.

The development of regenerative medicine has brought hope to these neuron cells missing in Parkinson's, and the use of stem cells to replace these cells has become the focus of research in the scientific community.

So how do existing stem cell therapies work?

Neurons are not a naturally renewing resource, they need to be replenished through external means, here is a brief overview of how the process works:

1. The researchers started with pluripotent cells, which are usually produced from skin cells or blood cells;

2. They differentiate pluripotent stem cells into brain-specific cells (e.g., dopaminergic progenitor cells);

3. They cultured differentiated cells to a critical mass in the laboratory;

4. They infused large numbers of stem cells into the patient's brain.

This "universal" method can indeed achieve the curative effect of stem cells and has brought hope to Parkinson's patients, but it is difficult to realize mass standardized production, so scientists have made new attempts.

A cell replacement therapy conducted by a research team led by Kim Joo-pyung, professor of neurosurgery at CHA University Bendang Medical Center (CBMC), South Korea, produced dopamine neural precursor cells from stem cells derived from the fetal midbrain, and then transplanted the dopamine neural precursor cells into the patient's brain.

They injected three different doses of cells (4×10 6 , 12×10 6 , 40×10 6 cells) into 15 patients under the age of 70 and followed them up for 12 months.

RESULTS: According to the Unified Parkinson's Disease Rating Scale (UPDRS), pronation-supination and hand/arm motor performance were significantly enhanced (P<0.05) in all three groups, with motor performance restored by 11.6% in the low-dose group, 26% in the mid-dose group, and 40% in the high-dose group at 12 months. Furthermore, there are no side effects such as bleeding, immune rejection, inflammation and tumor formation .

According to the results of the study, CHA University mass-produced dopamine precursor cells and applied them to patients, confirming the effect of using fetal stem cells to treat Parkinson's.

In particular, a 65-year-old woman with mid-stage Parkinson's disease received the world's first fetal stem cell transplantation for Parkinson's disease in 2013. She is now able to carry out daily activities and her overall motor function has improved, such as using public transportation normally.

This is a very encouraging result. The safety and effectiveness of dopamine neural progenitor cell transplantation were confirmed by PET-CT examination, and the good effect of inhibiting the progression of Parkinson's disease was observed in the long-term follow-up study of more than 10 years. If this therapy can be marketed, it will accelerate the development of stem cell therapy for Parkinson's disease.

Stem Cells Crack the Problem

Stem cells, induced under certain conditions in vitro, can differentiate into various types of cells, including neurons, an important property because Parkinson's disease is caused by the loss of melanin neurons in the brain, which also places the only hope for Parkinson's disease on stem cells.

In fact, the research on stem cell therapy for Parkinson's disease has a long history. As early as the 1980s, scientists have been exploring the possibility of stem cell therapy for Parkinson's disease. In recent years, many researchers have conducted trials using stem cells to treat Parkinson's disease, with encouraging results.

In August 2017, Japanese scientists published a study in the journal "Nature" that proved that dopamine precursor cells can improve the symptoms of Parkinson's disease in monkeys. By converting iPS cells from healthy people and Parkinson's patients into dopamine-producing neurons, they were implanted into rhesus monkey models with Parkinson's disease.

The results showed that the implantation of iPS cells played the role of dopaminergic neurons in the midbrain , not only restored various motor functions of the sick monkeys, but also did not transform into any tumor within two years after implantation.

After successful experiments with iPS cells in monkeys, the Japanese government gave researchers the green light to conduct the first human clinical trials . In October of the same year, the researchers implanted 2.4 million dopamine precursor cells cultured from iPS cells into the left brain of a 50-year-old patient. The results of the study showed that the patient was in good condition and there were no major adverse reactions .

Similarly, in 2020, an article published in the authoritative international journal "NEJM" also confirmed that transplanting iPSC-derived midbrain dopaminergic progenitor cells can effectively improve Parkinson's disease.

In the study, a patient who had endured Parkinson's disease for 10 years received 2 cell transplants with an interval of 6 months, implanted into the putamen of the left hemisphere and the right hemisphere respectively, with a dose of 4 million cells per transplant. After 2 years of transplantation, the patient's motor evaluation and quality of life have been greatly improved .

Of course, there are also good results in domestic research progress.

In 2018, the team of Professor Chen Zhiguo and Professor Zhang Yu from Xuanwu Hospital of Capital Medical University obtained human-derived induced neural stem cells (iNSC) through blood cell reprogramming, and verified the safety and effectiveness of this stem cell differentiation and transplantation in the treatment of Parkinson's disease through a mouse model, providing a preclinical basis for autologous cell therapy for patients with Parkinson's disease.

In June of the same year, the scientific research team of academicians of the Chinese Academy of Sciences tested the safety and effectiveness of human embryonic stem cell-derived nerve cells in the treatment of Parkinson's disease in a monkey model, and showed the evaluation data of up to 2 years, showing that the nerve cells differentiated from human embryonic stem cells are relatively safe and have obvious effects . Provided preclinical data support for my country's first phase I/II Parkinson's treatment clinical study based on embryonic stem cells.

Indeed, in the treatment of Parkinson's disease, the use of stem cells can rebuild lost dopamine neurons and thus alleviate the disease. The continuous progress and development of stem cell technology has also brought many opportunities and prospects to medicine. Stem cells have the ability to self-renew and differentiate into different cell types, so they can be used to treat various diseases, such as heart disease, diabetes, and various degenerative diseases .

However, the clinical application of stem cell technology still faces many challenges and difficulties, such as stem cell source, long-term monitoring of safety and effect, etc. Therefore, we need to continuously innovate and improve technology, while strengthening supervision and regulation to ensure the safety and effectiveness of stem cell technology.

In general, the development of stem cell technology is an important direction in the medical field. It is expected to bring more benefits and well-being to human beings, but it also requires our continuous exploration and improvement to achieve its wider clinical application.