Stem Cells Implanted into Patient with Parkinson’s Disease

Parkinson's is a neurodegenerative condition caused by the death of cells called dopaminergic neurons, which make a neurotransmitter called dopamine in certain areas of the brain. Scientist at Kyoto University have been developing iPS cells that produce the neurotransmitter dopamine. It is first important to understand what iPS cells are and how they function. iPS cells, short for induced pluripotent stem cells, are adult skin or blood cells that have been reverted back to their embryonic form. This is done by introducing genes that are important for maintaining the essential properties of embryonic stem cells into the skin cells. This then reverts them back into a pluripotent state. As many know, stem cells can give rise to any type of cell in the body through differentiation. Thus, after these iPS cells are made, they are introduced with DNA to give rise to these dopamine producing neurotransmitters. Previous trial had been run on monkeys with their own from of Parkinson's disease to test the viability of the iPS neurotransmitters. After two years of review, the monkeys did not show any adverse effects and their cells did not degenerate. The first human trial was conducted this past October; Dr. Takayuki Kikuchi implanted over 2.4 million dopamine precursor cells into a patient in his 50's. These cells were implanted in 12 different sites known to be centers of dopamine activity. As of November, the patient is doing well and there have been no adverse effects. If all goes well in the preliminary trials, this could be used as a treatment as early as 2023.

    

This was an interesting article to read. I found it interesting that they used so many of these iPS cells, presumably they must have identified how many they need to actually create a difference in the body. It is also important to understand that they can not administer too many of these cells because very high level of dopamine can make these patients psychotic, however to low of levels won't show a change. This just shows how quickly medicine is advancing and how important the understanding of the genome is because without it, creating these artificial cells wouldn't be possible.

Monkeys with Parkinson's disease benefit from human stem cells

A article on science daily was published regarding how monkeys with Parkinson's disease are benefiting from human stem cells.

Parkinson's disease degenerates cells in the brain known as dopaminergic (DA) neurons. When the symptoms of Parkinson's are found, it most likely appears that more than half of the DA neurons are lost in the brain of the individual. Neurosurgeons are planning on using DA neurons created from iPS cells to treat these patients with the disease. iPS cells are made from blood and skin cells which makes them easily obtainable. This idea is being tested for its safety and reliability, so they are trying the experiment on monkeys that have Parkinson's by transplanting the new cells in the monkeys brains.

I believe this could be a remarkable and cheap breakthrough if it works. Scientists were usually using fetal tissue to create DA neurons . Studies mentioned on how the transplant of these cells aid and help relieve symptoms of the disease. But using fetal tissues in general is a controversial topic. The use of iPS cells can help substitute the use of fetal tissue to treat patients.

https://www.sciencedaily.com/releases/2017/08/170830132224.htm

http://www.nature.com/nature/journal/v548/n7669/full/nature23664.html?foxtrotcallback=true

Hidden Genetic Mutations in Stem Cells Could Weaken Therapeutic Benefit

A microscopic image of human induced pluripotent stem cells (iPS). 

Mutations in mitochondrial DNA occur more frequently in individual cells as the human body ages. Since there are thousands of mitochondrial mutations and most of them are hidden, researchers have a hard time identifying all of the mutations present in a sample of a blood or piece of skin. However, researchers are able to distinguish the mutations easier if they are in iPS cells. In order to identify these mutations, iPS cells undergo a process where they are cloned in skin or blood cells which results in a iPS cell line that contains the same mitochondrial DNA mutations as the original adult cell. 

In a study conducted by Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University, researchers analyzed mitochondrial DNA mutations in 20 iPS cloned cell lines per patient that were obtained from blood and skin samples from healthy people and people suffering from degenerative diseases. When the iPS cell lines were sequenced, the researchers discovered that there was a significantly high number of mitochondrial mutations in the cells of patients who were over 60 years old. Based off of the results, the researchers observed that the larger the number of mutations in mitochondrial DNA caused a greater compromise to be made in the cells functions. Additionally, any defects in the mitochondria can potentially weaken or diminish the iPS cells ability to repair damaged tissues and organs. From this study the team of researchers discovered that iPS cells, specifically a type of stem cell from blood or skin sample, contain mutated mitochondrial DNA. In order to effectively use iPS cells to their full potential in humans, medical geneticist Taosheng Huang suggests that doctors and researchers need to check first if there are any mutations in the mitochondrial genome (Oregon Health and Science University 2016). 

I think that potential therapies involving the use of iPS stem cells can be used to treat diseases that occur with old- age. In the article, Mitalipov expressed that "pathogenic mutations in our mitochondrial DNA have long been thought to be a driving force in aging and age- onset diseases, though clear evidence was missing. Now with that evidence at hand, we know that we must screen stem cells for mutations or collect them at a younger age to ensure their mitochondrial genes are healthy" (Oregon Health and Science University 2016). In my opinion, I think the background knowledge of how cells are damaged with old age can serve as a basis for future studies to further examine how mutations in the mitochondria play a role in degenerative diseases. 

Parkinson's Disease in a Dish

Credited to a combination of genetic and nongenetic aspects, Parkinson’s disease has no completely effective therapy or cure. Parkinson’s disease is reasonably heritable, but the mechanism of this inheritance is not well understood. While genetic forms of the disease occur, random forms are far more common. A team of scientists managed by The New York Stem Cell Foundation (NYSCF) Research Institution successfully produced a human stem cell disease model of Parkinson’s disease in a dish. Studying a pair of identical twins, one affected and one unaffected with Parkinson’s disease, another unrelated Parkinson’s patient, and four healthy control subjects, the scientists were able to notice crucial features of the disease in the laboratory, specifically variances in the patients’ neurons’ capability to create dopamine, the molecule that is lacking in Parkinson’s disease. In addition, the scientists also acknowledged a possible approach for developing innovative therapies for Parkinson’s disease.

DNA mutations resulting in the production of a specific enzyme termed glucocerebrosidase (GBA) have been connected to a five-fold greater risk of developing Parkinson’s disease; conversely, only 30% of individuals with this mutation have been exposed to developing Parkinson’s disease by the age of 80. This discordance proposes that several factors contribute to the development of Parkinson’s disease as well as both genetic and non-genetic factors.

In this study, a pair of identical twins, both with GBA mutation, delivered a unique opportunity to evaluate and separate the genetic and non-genetic influences to the development of Parkinson’s disease in one twin, and the absence of disease in the other twin. The scientists made induced pluripotent stem (iPS) cells from skin samples from both twins to produce a cellular model of Parkinson’s in a dish, reiterating crucial features of the disease, specifically the growth of alpha-synuclein and dopamine absence.

Upon investigating the cell models, the scientists found that the dopamine-producing neurons from both twins had reduced GBA enzymatic activity, raised alpha-synuclein protein levels, and a reduced ability to synthesize and release dopamine. In contrast to his unaffected brother, the neurons generated from the affected twin produced less dopamine, had higher levels of an enzyme called monoamine oxidase B (MAO-B), and deprived capability to connect with each other. Treating the neurons with molecules that lowered the activity of MAO-B together with overexpressed GBA helped normalize alpha-synuclein and dopamine levels in the cell models. This proposed that a combination therapy for the affected twin may be probable by simultaneously targeting these two enzymes.

Although this is an innovating study, the genetic and stem cell analysis identified an avenue for a potentially useful combination therapy for the twin affected by Parkinson’s disease. This study could be useful for other Parkinson’s patients. To me, the this research and cellular analysis is useful to further clues to all cases of genetic and sporadic Parkinson’s disease and other neurological disorders.

Article- http://www.sciencedaily.com/releases/2014/11/141106132208.htm

Diseases in A Dish

Human diseases are often hard to treat due to the regulations on human testing and the years of clinical research to get FDA approval. How ever there is a new technological breakthrough that is allowing the culturing of human cells in a petri-dish, so they can be experimented on. This is all possible by the newly developed induced pluripotent stem cells or iPS cells.

These iPs cells were recently developed by Shinya Yamanaka, a Japanese scientist who created them from taking ordinary cells and putting them through a process that allowed them to go back to a stem cell like phase. Stem cells are so important because they are harvested at a stage where they have the capability to grow into any type of cell in the body with the right manipulation. However, due to there source, unborn babies, they have been outlawed to use in several countries. So with this accomplishment, the use of embryonic stem cells has become obsolete. Scientists in Germany have recently used iPs cells to create cardiac tissue that has a pulse and beats on its own, within a petri-dish. Science can now continue on in an extraordinary way.



This break through is one that has immense potential in the scientific field. Shinya Yamanaka recently won the noble prize for his work with iPS cells and I believe it will allow research that will lead to many diseases being cured.  iPs cells will have tremendous value in the years to come, and they will be instrumental in our understanding of biology.