Research on stem cells is advancing knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. This promising area of science is also leading scientists to investigate the possibility of cell-based therapies to treat diseases that are typically referred to as regenerative or reparative medicine. Regenerative medicine aims at helping the body to form new functional tissues to replace lost or defective ones. Hopefully, this will help to provide therapeutic treatment for conditions where current treatment modalities are inadequate. Human body has an endogenous system of regeneration through stem cells, where stem cells are found almost in every type of tissue. The popular notion is that restorations of functions are best accomplished by these stem cells. Regenerative medicine comprises the use of tissue engineering and stem cell technology. This review is not meant to be exhaustive, but aims to highlight present and future applications of stem cells in this exciting new emerging discipline.
- CLINICAL APPLICATIONS
The economic and psychological burdens of chronic, degenerative, and acute diseases in the world are enormous. It has been estimated that up to many millions of people suffer from such diseases either directly or indirectly. As more research takes place, the developmental potentials of different kinds of stem cells will become better understandable. As per our current understanding, adult stem cells are limited in their potential to differentiate.
However, embryonic stem cells have a great differentiation capacity, and are thought to be able to differentiate into almost any types of tissue. Thus, different types of stem cells isolated from different tissues could have different applications. The potential applications of stem cells are discussed below.
2.1 Nervous system diseases:
Many nervous system diseases result from loss of nerve cells. Mature nerve cells cannot divide to replace those that are lost. Thus, without a new source of functioning nerve tissue, there won’t be any therapeutic possibilities. Thus neural stem cells could be good tool for the regeneration of new neurons.
2.1.1 Parkinson’s disease:
In this disease, nerve cells that make the neurotransmitter dopamine die. Dopamine is chemical that allows messages to be sent to the parts of the brain that controls movement and some forms of thinking. The traditional method of treatment includes the drug Levopoda, which was discovered in the 1960s that substitutes the action of dopamine in the body but doesn’t slow down or reverse the damage caused to the nerve cells in the brain. Although the underlying cause of Parkinson’s disease (PD) is unknown, scientists do know which cells and areas of the brain are involved. Researchers are already using stem cells to grow dopamine-producing nerve cells in the lab so that they can study the disease, especially in those cases where there is a known genetic cause for the condition. Because a single, well-defined type of cell is affected, it may also be possible to treat Parkinson’s by replacing the lost nerve cells with healthy new ones.
Doctors and scientists think replacement therapy will work because of the results of transplantation studies done in 1980s -90s. Scientists remain optimistic that introducing young cells into the brain could better treat Parkinson’s disease, but not enough fetal tissue is available to treat the large numbers of people with PD, and the use of fetuses also raises ethical questions.
So at the same time, they are looking at adult stem cells as an alternative source of new dopamine cells for Parkinson’s patients:
Embryonic stem (ES) cells could be directed to make dopamine-producing neurons, which could be transplanted into patients. Dopamine-producing neurons have been made from both mouse and human embryonic stem cells in the laboratory, and the human cells have recently been shown to have similar effects as the fetal cells in a rat model of Parkinson’s disease.
Induced pluripotent stem (iPS) cells could be made from a patient’s adult skin cells in the lab, and then used to make dopamine-producing neurons. In 2010 scientists in the USA treated rats with neurons made from human skin cells using iPS techniques. The transplanted neurons improved features of Parkinson’s disease in the rats. However, mice and rats require fewer neurons than humans and it is not yet clear whether this approach would work in patients. More studies are also needed to make sure the cells are safe and would not cause tumors in the brain, and also do not rapidly develop the pathology of Parkinson’s given they are derived from the patients themselves.
2.1.2 Alzheimer’s disease
In Alzheimer’s disease, the cells that are responsible for the production of certain neurotransmitters die. Alzheimer’s is the most common form of dementia. The first sign of Alzheimer’s often include lapses on memory or struggling to find the right words. Overtime, symptoms include confusion, mood swings or memory loss develop and become increasingly severe. Currently there is no permanent cure for this disease but for temporary cure there are certain drugs administered that help in improving the memory or ability to manage the everyday tasks. Most of these drugs belong to a class called cholinesterase inhibitors (e.g. Aricept, Exelon, Reminyl). These drugs can help prevent the breakdown of a natural substance in the brain called acetylcholine, which carries signals between neurons. However, there are no drugs that delay or halt the loss of neurons.
However there are no stem cell treatments available yet but scientist are engaged actively in the research on stem cell transplants in mice and studies have shown some benefits. Another possible approach to stem cell therapies might be use of certain types of stem cells to deliver proteins called neurotrophins to the brain as these proteins help in supporting and sustaining the growth of neurons in a healthy brain. These are produced in lower levels in the Alzheimer’s patient.
2.1.3 Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis is a progressive fatal neurodegenerative disease that targets motor neurons. Its origin is unknown but a main role of reactive astrogliosis and microglia activation in the pathogenesis has been recently demonstrated. Surrounding neurons with healthy adjoining cells completely stops motor neurons death in some cases. Many compounds directed at the potential targets have been tested for their effects on ALS. Riluzole (2-amino-6-trifluoromethoxy benzothiazole, also called Rilutek), a member of the benzathiole class, is the only available successful medication. Unfortunately, it has so far been only proven to slow disease progression in ALS on average prolonging the ALS patient’s life only 3 months. Hence stem cells transplantation might represent a promising therapeutic strategy. The development of relevant therapies for ALS has proven to be challenging particularly because of the insidious, neurodegenerative course of the disease. Thus in order to treat ALS, degenerating motor neurons ultimately need to be protected, regenerated or replaced. Stem cell therapy is an innovative approach for ALS treatment given the ability of stem cells to differentiate into multiple neuronal lineages. There are different types of stem cells used for the ALS treatment: human umbilical cord blood derived-cells, embryonic stem cells,
Induced pluripotent stem cells, mesenchymal stem cells, and neural stem cells.
2.1.4 Spinal cord injury
The spinal cord is the delicate tissue encased in and protected by the hard vertebrate of the spinal column. It is made up of millions of nerve cells that carry signals to and from the brain and out into the other parts of the body.
A spinal cord injury is a devastating and debilitating condition affecting the people all over the world, particularly young adults affecting both neurons and the myelin sheath that insulates axons.
They are associated with severe physical, psychological, social and economic burdens on patients and their families. Despite the important advances in the understanding of spinal cord injuries, to date, almost all therapies that have shown promise at the preclinical stage of study have failed to translate into clinically effective treatments. The environment of the spinal cord changes drastically during the first few weeks after injury. Studies in animal have shown that a transplantation of stem cells or stem cells derived cells may contribute to spinal cord repair by:
- Replacing the nerve cells that have died as a result of injury
- Generating new supporting cells that will re-form the insulating nerve sheath (myelin) and acts as a bridge across the injury to stimulate re-growth of damaged axons.
- Protecting the cells at the injury site from further damage by releasing protective substances such as growth factors and soaking up toxins such as free radicals, when introduced into the spinal cord shortly after injury.
- Preventing spread of the injury by suppressing the damaging inflammation that can occur after injury.
There are many clinical trials undergoing in many research institutes and universities in Germany, USA and Europe using neural stem cells, Mesenchymal stem cells, and embryonic stem cells.
2.1.5 Multiple sclerosis
Multiple sclerosis (MS) is a disease that affects the nerve cells in the brain and spinal cord. In the healthy body, these nerve cells carry messages between the brain and rest of the body. In MS, the body’s own immune system attacks the nerve cells so that they cannot function properly. There is currently no cure for multiple sclerosis but it is possible to treat the symptoms and reduce the number pf relapses using medicine, exercise and physiotherapy.
These treatments aim to help patients cope with symptoms or try to prevent damage to the nerve cells, but they do not help repair damage once it has occurred. Researchers hope that stem cells therapies may provide new approaches that can both prevent damage and enable us to repair it. There are several different types of stem cells and scientists are investigating a number of ways they might be used to develop new treatments for multiple sclerosis by preventing damage and repairing damage and developing new medicines. The various approaches offer different advantages and may be useful for treating different types or stages of MS. For preventing damage blood stem cells, Mesenchymal stem cells, for repairing damage neural stem cells and for studying disease and developing drugs embryonic stem cells and induced pluripotent stem cells are being used currently. Although stem cells are very useful in MS disease research currently they are not available for the treatment
To be continued…
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