Stem Cells Help In Identifying New Treatments for Dementia

Researchers in Belgium are using induced pluripotent stem cell (iPSC) technology to create neurons that are targeted by dementia.

By studying these neurons, the scientists have found a defect that prevents normal neurodevelopment. Stem cells were taken from patients who has an inheritable type of dementia that is responsible for 50% of dementia cases for people below the age of 60.

Dementia is a neurological disorder that causes loss of brain function. Memory, language, behavior, judgement and how the patient thinks are affected by dementia. It is a serious loss of global cognitive ability in a previously unimpaired or normal person, beyond what might be expected from normal aging. It may be static dementia, the result of a unique global brain injury, or progressive dementia, resulting in long-term decline due to damage or disease in the body.

The most common type of dementia is Alzheimer's disease.

Usually associated with elderly patients, there are cases of dementia occurring to patients below the ages of 60/65.

The type of dementia that the Belgian scientists are studying is frontotemporal dementia. It is the result of damaged neurons in the frontal and temporal lobs which affects the patient's behavior, language, and emotions.

By reconstructing the damaged neurons using stem cells, the scientists identified the defective neuron pathway, the Wnt signalling pathway, that when genetically corrected and treated, restored the ability of the iPSCs to turn into cortical neurons.

This novel method may help scientist better understand the disease and create a cure or therapy for the disease.

Cellular Reprogramming In Treatment of Multiple Sclerosis, Cerebral Palsy and other Myelin Disorders.

Researchers have successfully converted fibroblasts (a structural cell) into oligodendrocytes which could regenerate new myelin coatings around nerves. This treatment can be used in myelin related disorders such as multiple sclerosis and cerebral palsy.

Cellular Reprogramming is a technique that allows the conversion of one type of cell into another. Although it shares a similar concept with stem cell technolgy, unlike stem cell therapy, cellular reprogramming utilizes direct manipulation of the cell at a genetic level to convert it into another type of cell.

Stem cells naturally differentiate into another type of cell. In 2012, Doctor Shinya Yamanaka won the Nobel Prize in Physiology or Medicine for his research on generating induced pluripotent stem cells (iPS cells) through cellular reprogramming. iPS cells are pluripotent stem cells that are artificially derived from normal cells.

Scientists Speed Up and Increase Efficiency In Production of Induced Pluripotent Stem Cells

Induced pluripotent stem cells generated using a kinase inhibitor.
Credit: Sanford-Burnham Medical Research Institute

To understand stem cells, there are two terms that are important to understand; pluripotency and differentiation.

Differentiation is the process in which the cell can transform itself into a higher class or specialized type of cell.

Pluripotency in stem cell biology means that the cell can differentiate itself into three types of germ layers: the endoderm, the mesoderm, and the ectoderm. The term "germ layer" more or less refers to the tissue layer. A group of germ layers eventually form tissues and organs of the body.

These three germ layers a stem cell can differentiate into, form much of the human body's organs. The endoderm forms into the internal organs such as the lungs, stomach lining, and the intestinal tract. The Mesoderm forms muscle and bone groups while the ectoderm forms epidermal tissues and the nervous system.

Because the stem cell can differentiate into other type of cells, there is much focus on this field for medical research. Stem cell research can open up new and effective treatments for otherwise difficult conditions such as alzheimers, parkinsons, cardiovascular diseases, and even cancer.

Early in stem cell research, a primary source for these type of cells were embryonic stem cells. These cells came from human fertilized eggs that are about four to five days old. Because of the manner of this process, there are moral issues that were raised with regards to these type of cells.

A recent technology introduced another way to source stem cells. These are called induced pluripotent stem cells or iPSC. These are artificially produced stem cells from non-pluripotent cells. The process is done by inducing or activating dormant genes within the cell to activate its pluripotency.

Making it easier to make stem cells

The process researchers use to generate induced pluripotent stem cells (iPSCs)—a special type of stem cell that can be made in the lab from any type of adult cell—is time consuming and inefficient. To speed things up, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) turned to kinase inhibitors. These chemical compounds block the activity of kinases, enzymes responsible for many aspects of cellular communication, survival, and growth. As they outline in a paper published September 25 in Nature Communications, the team found several kinase inhibitors that, when added to starter cells, help generate many more iPSCs than the standard method. This new capability will likely speed up research in many fields, better enabling scientists around the world to study human disease and develop new treatments.

"Generating iPSCs depends on the regulation of communication networks within cells," explained Tariq Rana, Ph.D., program director in Sanford-Burnham's Sanford Children's Health Research Center and senior author of the study. "So, when you start manipulating which genes are turned on or off in cells to create pluripotent stem cells, you are probably activating a large number of kinases. Since many of these active kinases are likely inhibiting the conversion to iPSCs, it made sense to us that adding inhibitors might lower the barrier."