Roundtable Review

Biology Basics: What’s the deal with stem cells?
Posted 05 February '13

Microscope view: stem cells reprogrammed from adult skin cells.
Attribution: Penn State, Source: Under License: Creative Commons Attribution-NonComercial-NoDerivs 2.0 Generic

Stem cells – those two little words have generated a lot of publicity in the past few years. Although they seem like a relatively new ‘hot topic’, scientists have been interested in cell biology since microscopes were discovered in the 1800’s. It has been about 200 years since cells were recognized as the building blocks of life, propagation and differentiation were witnessed, and the conclusion that cells were capable of giving rise to other cells and key to understanding human development.

Stem cells are unspecialized, undeveloped, rapidly growing cells that can reproduce themselves and grow into new tissue. Studying stem cells will allow us to better understand how they transform into an array of specialized cells that make us what we are. According to the Human Tissue Authority (HTA) there are about 210 different types of human tissue that originate from these primitive cells. Medical conditions, such as cancer and birth defects, are due to problems that occur somewhere in this process. A better understanding of normal cell development will allow us to understand and perhaps correct the errors that cause these medical conditions. Another potential application of stem cells is making cells and tissues for medical therapies. Donated organs and tissues are often used to replace those that are diseased or destroyed in others. Unfortunately, the number of people needing a transplant far exceeds the number of organs available for transplantation. Scientists believe that healthy stem cells can be introduced into a patient to restore lost function to damaged organs, especially the brain, due to the fact that stem cells have the potential to grow into almost any kind of tissue, including nerves, bones, and muscle. Stem cells are also beginning to be used for modeling human disease, and to aid in drug development.

Where did the did the idea of stem cells originate?

About 100 years ago European researchers discovered that the various types of blood cells all came from a particular ‘stem cell’. However it was not until 1963 that two Canadian scientists, Ernest A. McCulloch and James E. Till, documented descriptions of the self-renewing activities of transplanted mouse bone marrow cells. Research into adult stem cells in animals and humans has been ongoing since this time, and bone marrow transplants (which are actually a transplant of adult stem cells) have been used in patients receiving radiation and chemotherapy since the 1950’s. Stem cells are the parent cells for all tissues and organs of the body, and they exist mainly to maintain and repair cells in the areas where they are found (blood, bone marrow, skin, muscle, and organs such as the brain and liver). Blood-forming stem cells are present in umbilical cord blood and the placenta, and can be extracted from the discarded tissues at birth.

The ‘80’s and ‘90’s saw ground-breaking developments in biotechnology, particularly in techniques for targeting and altering genetic material, as well as in methods for growing human cells in the laboratory. This was really the beginning of human stem cell research. In 1998 James Thomson, a scientist at the University of Wisconsin in Madison, successfully removed cells from spare embryos at fertility clinics and grew them in the laboratory. This essentially propelled stem cell research into the public eye, as he established the world’s first human embryonic stem cell line – which still exists today. Embryonic stem cells are not derived from eggs fertilized in a woman’s body; they are always generated from fertilized, frozen eggs originating from fertility clinics. Fully informed donors can donate these embryos to research if they no longer desire additional children, do not wish to continue storage or do not wish to give them up for adoption. If these excess embryos are not used for research, they are destroyed. Embryonic stem cells can become any cell type of the body and are therefore more versatile than adult stem cells. The disadvantage is that they are likely to be derived from donor embryos, meaning the patient’s body may reject them following transplantation.

How do stem cells work?

Generally speaking, there are two ‘native’ types of mammalian stem cells: embryonic cells that are found in blastocysts and adult stem cells that are found in adult tissues. In the developing embryo, stem cells can differentiate into any type of embryonic tissues, however in the adult organism progenitor and stem cells act as a repair system for the body by replenishing cells and maintaining tissues and organs. Stem cells form in the center of large bones, the bone marrow, by receiving chemical signals that direct it to become an erythrocyte, leukocyte, or a small cluster of platelets. Once mature, the cells are released into the peripheral blood stream. The adult stem cells stay localized to a specific area of each tissue where they constantly replicate to maintain a supply of cells. Stem cells can be identified by using methods that assess their ability to differentiate and self-renew, as well as identifying a distinctive set of cell surface markers.  In order to make an embryonic cell line, a group of stem cells grown in the lab that can self-renew and grow new cells indefinitely, an embryo needs to be stripped of its outer layer of protective cells then placed into a special culture. Cell lines created from adult stem cells are typically created by chemically forcing adult cells to revert to a state similar to that of an embryonic stem cell.

Where are we today?

Stem cell research has been progressing ever since, and every year thousands of research papers are published in scientific journals. Evidence has emerged to suggest that embryonic stem cells are capable of becoming almost any specialized cell in the body, and as such have the potential to generate replacement cells for tissue and organs such as the heart, liver, pancreas and nervous system. Although embryonic stem cell research has not yielded any clinical trials yet, adult stem cells have been used in treatments for some time. Most adult stem cells are pre-specialized; for example blood stem cells make only blood. That being said, recent advances have led to a new technique that has made it possible to create adult stem cells which can form many kinds of tissue – these are called induced pluripotent stem cells (iPSCs). The major potential advantage of this technique is the possibility of patients using their own cells for treatment.

According to the Medical Research Council in the UK, there have been great achievements in our own backyard. Scientists at the UCL Institute of Child Health are beginning to influence stem cells within the body, specifically cells in the outer layer of the heart have been shown to migrate inside and assist in repairing a failing adult heart. Additionally, vision problems and blindness may be treatable with stem cell transplants, as UCL scientists have shown they can replace retinal cells in mice to restore vision.

Where are we going?

While some stem cell therapies already exist, mostly those involving bone marrow or cord blood transplantation for the treatment of some cancers, scientists and doctors believe that stem cells may be used in the future to treat certain genetic diseases, tissue injuries and degenerative diseases, including but not limited to spinal cord injury, stroke, Parkinson’s disease, diabetes, and heart disease. According to the US National Institutes of Health, stem cells can only be made useful for transplant purposes if they reproducibly proliferate extensively and generate sufficient quantities of tissue, differentiate into the desired cell type(s), survive in the recipient after transplant, integrate into the surrounding tissue after transplant, avoid harming the recipient in any way, and function appropriately for the duration of the recipient’s life. While promising results from animal studies have served as the basis for a small number of exploratory studies in humans, significant technical hurdles still remain that will only be overcome through years of intensive research. As such, promising basic and clinical research must be supported to fully realize the possibilities and potential for stem cells.

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