Part I: A brief description of the Early Life Issues
3. Stem Cells
Stem cells are found in all multicellular organisms and are produced by the human body from the earliest stages of its prenatal development. They combine the ability to reproduce indefinitely through mitotic[1] cell division and to differentiate[2] into particular types of tissue. The existence of stem cells has been known since the 1960’s, when they were discovered by a pair of Canadian scientists, Ernest A. McCulloch and James E. Till.
These undifferentiated cells have been found to have varying degrees of plasticity[3]. Stem cells are present in the human body throughout the person’s lifespan and, together with progenitor cells[4], act to repair damaged tissue. So-called “adult” stem cells are those produced in the body throughout the individual’s post-natal lifespan. They are abundantly produced by the bone marrow but are increasingly being discovered in other tissue sources.
There currently exist many therapeutic applications of adult stem cells. Treatments exist for some forms of cancer that involve screening stem cells from the patient’s blood and re-inserting them into the body. Such treatments avoid the problem of tissue rejection and have led to research into replacing entire organs from the patient’s own cells.
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 is often referred to as regenerative or reparative medicine.
What are Stem Cells? [5]
Stem cells are undifferentiated, or unspecialised cells that have the ability both to renew themselves by cell division for long periods and, under certain physiologic or experimental conditions, can be induced to become cells of a particular type of tissue such as the beating cells of the heart muscle or the insulin-producing cells of the pancreas.
Two broad categories of stem cells are known: those derived from human beings at the embryonic stage of life, usually called “embryonic stem cells” in the media, and those derived postnatally, often called “adult stem cells.” Scientists discovered ways to obtain or derive stem cells from early mouse embryos more than 20 years ago. In 1998 a method was discovered to isolate stem cells from living human embryos and grow the cells in the laboratory. These are called human embryonic stem cells, usually[6] taken from embryos created in fertility clinics through in vitro fertilization and donated for research.
Factors Common to all Stem Cells
One of the fundamental properties of any type of stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. A stem cell cannot work with its neighbors to pump blood through the body (like a heart muscle cell); it cannot carry molecules of oxygen through the bloodstream (like a red blood cell); and it cannot fire electrochemical signals to other cells that allow the body to move or speak (like a nerve cell). However, unspecialized stem cells can give rise to specialized cells, including heart muscle cells, blood cells, or nerve cells.
All stem cells are capable of dividing and renewing themselves for long periods. Unlike muscle cells, blood cells, or nerve cells—which do not normally replicate themselves—stem cells may replicate many times. When cells replicate themselves many times over it is called proliferation. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal.
Human Embryonic Stem Cells [7]
Embryonic stem cells are usually derived from a four or five days old embryo. The embryo at this stage is a ball of cells called the blastocyst. The blastocyst includes three structures: the outer ball, called the trophoblast, that will later form the placenta and supporting structures for the child after implantation; the blastocoel, which is the hollow cavity inside the blastocyst; and the inner cell mass, which is a group of approximately 30 pluripotent cells called blastomeres that will develop into all the tissues and structures of the child’s body.
Human embryonic stem cells are isolated by removing the inner cell mass from the embryo and transferring it into a plastic laboratory culture dish that contains a nutrient broth known as culture medium. The original embryo dies when the inner cell mass is removed.
The cells then divide and spread over the surface of the dish. The inner surface of the culture dish is typically coated with mouse embryonic skin cells called a feeder layer that give the inner cell mass cells a sticky surface to which they can attach. The feeder cells convey nutrients into the culture medium.
After six months or more, the original 30 cells of the inner cell mass yield millions of embryonic stem cells. Embryonic stem cells that have proliferated in cell culture for six or more months without differentiating, are pluripotent, and appear genetically normal are referred to as an embryonic stem cell line.
Once cell lines are established, or even before that stage, batches of them can be frozen and shipped to other laboratories for further culture and experimentation.
Embryonic stem cells are pluripotent, meaning they are able to differentiate into all of the more than 220 cell types in the adult body. A pluripotent embryonic stem cell can form any of the three germ layers of the early term embryo: endoderm (that will develop the tissues of the interior stomach lining, gastrointestinal tract, lungs); the mesoderm (muscle, bone, blood, urogenital tissues); or ectoderm (epidermal tissues and nervous system).
The pluripotent stem cells derived from blastomeres cannot develop into a fetal or adult animal because they lack the potential to contribute to extraembryonic tissue, such as the placenta.
Totipotent (literally meaning “having all powers”) cells can develop as separate embryos. The zygote is considered totipotent because it will form both the foetal structures and the extraembryonic supporting structures. Totipotent stem cells can be derived from embryos that have not yet formed the trophoblast and can be induced to start dividing and developing as distinct embryos. This technique is called “blastomere separation” and is a form of cloning. It will be covered more fully in the section on cloning below.
The removal of one or more blastomeres from an embryo does not always cause the embryo’s death. This is often done as part of the process of pre-implantation genetic diagnosis in IVF.
Adult Stem Cells [8]
An adult stem cell is an undifferentiated cell found among differentiated cells in a tissue or organ, that can renew itself, and differentiate to yield the major specialized cell types of the tissue or organ. The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found. Some scientists now use the term somatic stem cell instead of adult stem cell. Unlike embryonic stem cells, which are defined by their origin (the blastomeres of the inner cell mass of the blastocyst), the origin of adult stem cells in mature tissues is unknown.
Stem cells are thought to reside in a specific area of each tissue where they may remain quiescent (non-dividing) for many years until they are activated by disease or tissue injury. The adult tissues reported to contain stem cells include brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin and liver.
Researchers are finding sources of adult stem cells in many more tissues than was once thought possible. This finding has led scientists to ask whether adult stem cells could be used for transplants. Certain kinds of adult stem cells seem to have the ability to differentiate into a number of different cell types, given the right conditions. If this differentiation of adult stem cells can be controlled in the laboratory, many researchers believe that these cells may become the basis of therapies for many serious common diseases and injuries.
In the 1960s, researchers discovered that the bone marrow contains at least two kinds of stem cells. One population, called hematopoietic stem cells, forms all the types of blood cells in the body. A second population, called bone marrow stromal cells, was discovered a few years later. Stromal cells are a mixed cell population that generates bone, cartilage, fat, and fibrous connective tissue.
Also in the 1960s, scientists discovered two regions of the brain that contained self-replicating cells which become nerve cells. By the 1990s scientists agreed that the adult brain contains stem cells able to generate the brain's three major cell types—astrocytes and oligodendrocytes, which are non-neuronal cells, and neurons, or nerve cells.
Since then the list of discoveries surrounding adult stem cell origins and their ability to form a wide variety of tissue types has grown almost daily. While embryonic stem cell research has yet to produce any actual therapeutic results, adult stem cells are becoming widely used in the treatment of numerous diseases and injuries and continue to yield promising experimental results related to many serious diseases.
Recent experiments have shown that certain adult stem cell types are pluripotent. The following list offers examples of adult stem cell plasticity that have been reported during the past few years:
- Hematopoietic stem cells may differentiate into: three major types of brain cells (neurons, oligodendrocytes, and astrocytes); skeletal muscle cells; cardiac muscle cells; and liver cells.
- Bone marrow stromal cells may differentiate into: cardiac muscle cells and skeletal muscle cells.
- Brain stem cells may differentiate into: blood cells and skeletal muscle cells.
Umbilical Cord Stem Cells [9]
Umbilical cords have traditionally been discarded as a by-product of the birth process. In recent years, however, the blood found in the umbilical cord has been found to be a rich source of multipotent stem cells, some of which have been found to have a plasticity approaching that of embryonic stem cells. Cord blood stem cells have yeilded therapeutic applications similar to those using bone marrow stem cells and peripheral blood stem cells. Private clinics are starting to be found around the world where clients can store umbilical cord blood as a preparation for possible future illness or accident.
Umbilical cord blood stem cell transplants are less prone to rejection than transplants from bone marrow cells. Because umbilical cord blood lacks well-developed immune cells, there is less chance that the recipient’s body will attack the transplanted cells.
Peripheral Blood Stem Cell Transplants
A method of replacing blood-forming cells destroyed by cancer treatment. Stem cells found in the circulating blood, similar to those in the bone marrow, are screened, typically from the patient’s own blood before treatment and replaced afterwards. This helps the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin).
During the research in the development of stem cell transplant therapies, it was discovered that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. From this was developed a method of obtaining stem cells from a patient’s blood.
Now, most hematopoeitic stem cell transplantation procedures are performed using stem cells collected from the peripheral blood, rather than from the bone marrow.
Other Uses of Stem Cells
In the section below, a few examples have been included showing recent breakthroughs and therapeutic applications of adult stem cells. These are only a tiny sampling of the hundreds of discoveries in the last ten years. Thus far, no successful application of embryonic stem cells have been found, although researchers continue to lobby heavily for their use in research.
Apart from use in treating diseases and injuries, human stem cells can also be used to test new drugs. New medications can be tested for safety on cells generated from human pluripotent (embryonic) cell lines that have been induced to differentiate into desired tissue types. Cell lines that are not derived from stem cells are already used in this way. Cancer cell lines, for example, are used to screen potential anti-tumor drugs.
Differentiation
Embryonic stem cells will remain undifferentiated as long as they remain isolated. If they are allowed to clump together they form “embryoid bodies” that begin to differentiate spontaneously and form various tissue types such as muscle cells, nerve cells, etc.
In order to obtain particular desired tissue types, scientists will change the chemical composition of the culture medium, alter the surface of the culture dish, or modify the cells by inserting specific genes. These techniques are referred to as “directed differentiation” the manipulation of stem cell culture conditions to induce differentiation into a particular cell type.
Immune System Rejection Problem
Tissue rejection occurs when the immune system of the recipient of a tissue transplant attacks the transplanted organ or tissue. This is because a normal healthy human immune system can distinguish foreign tissues and attempts to destroy them, just as it attempts to destroy infective organisms such as bacteria and viruses.
In conventional transplants with donated organs, immune supressant drugs must be taken by the recipeint indefinitely to suppress the body’s attempt to destroy the implanted organ. In stem cell applications, the immune system problem is especially acute in attempts to use embryonic stem cells, tissue derived from another person, directly in therapeutic applications.
One of the most important advantages of adult stem cell therapies is that the tissue involved comes from the patient’s own body, circumventing immune system rejection problems.
Key questions in Ongoing Research
The NIH website lists a number of important questions about adult stem cells researchers are currently exploring:
- How many kinds of adult stem cells exist, and in which tissues do they exist?
- What are the sources of adult stem cells in the body? Are they "leftover" embryonic stem cells, or do they arise in some other way? Why do they remain in an undifferentiated state when all the cells around them have differentiated?
- Do adult stem cells normally exhibit plasticity, or do they only transdifferentiate when scientists manipulate them experimentally? What are the signals that regulate the proliferation and differentiation of stem cells that demonstrate plasticity?
- Is it possible to manipulate adult stem cells to enhance their proliferation so that sufficient tissue for transplants can be produced?
- Does a single type of stem cell exist—possibly in the bone marrow or circulating in the blood—that can generate the cells of any organ or tissue?
- What are the factors that stimulate stem cells to relocate to sites of injury or damage?
- What are the factors that stimulate stem cell proliferation in the body’s tissues?
Some Recent Therapeutic Applications and Experimental Results with Adult Stem Cells[10]
February 2005 [11]: A research team led by University of Central Florida professor Kiminobu Sugaya has discovered a compound related to DNA that could improve the results of stem cell treatments for Alzheimer’s patients. The research team found that treating bone marrow cells with the compound made adult stem cells more likely to turn into brain cells in experiments with rats.
February 2006 [12]: 48 people diagnosed with the autoimmune condition known as systemic lupus erythematosus (lupus) received an experimental therapy from Chicago’s Northwestern Memorial Hospital, using a stem-cell transplant from their own bone marrow. At the time of the report, thirty-three of the patients treatment remained in complete remission.
November 2006 [13]: Newcastle University researchers Nico Forraz and Colin McGuckin grew ‘mini-livers’ using stem cells obtained from umbilical cord blood. The tissue is capable of being used to test new drugs and, in future years, of providing life-saving treatment to patients in need of liver transplants.
November 2006 [14]: University College London Hospital, St. Bartholomew’s and the London NHS will treat heart attack victims with an injection of adult bone marrow stem cell treatment. Patients suffering a heart attack will undergo regular treatment of an angioplasty to remove blockage to an artery, and then will receive an injection into the artery of stem cells harvested from the bone marrow in their hip, under local anesthetic. The treatment has shown remarkable success in growing heart tissue, in trials in other countries. Doctors hope the technique will lead to repairing damaged heart muscles and preventing further attacks and the development of heart failure.
January 2007 [15]: Researchers in New York have successfully generated new tooth roots and supporting ligaments in pigs, using human adult stem cells taken from extracted wisdom teeth. The regenerated tooth was used to support a crown restoration in miniature pigs, Reuters reported. The tooth exhibited the same functional and strength characteristics of the original tooth.
February 2007 [16]: Dr. Francisco Fernandez-Aviles, Professor of Cardiovascular Medicine and Chief of Cardiology Service at Gregorio Marañón and Dr. Perin, Director of New Interventional Cardiovascular Technology and Director of Stem Cell Center at the Texas Heart Institute at St. Luke’s Hospital, used human adipose (fat) tissue as a source of adult stem cells to regenerate damaged heart muscle. After processing, the stem cells were injected directly into the patient’s heart, targeting areas of damaged but still viable tissue.
“This is the first time we have used adipose-derived stem cells in humans. We had good results in our pre-clinical tests and we are excited about taking this research to the next level,” said Dr. Perin.
April 2007 [17]: A man's vision was restored by a corneal patch grown from his own stem cells by a team at the University of Melbourne's Centre for Eye Research Australia (CERA) and the Bernard O'Brien Institute of Microsurgery (BOBIM).
May 2007 [18]: Researchers at the University of Texas engineered adult stem cells derived from human umbilical cord blood to produce insulin. Published in the June 2007 issue of the medical journal Cell Proliferation, the paper calls it "the first demonstration that human umbilical cord blood-derived stem cells can be engineered" to synthesize insulin. "This discovery tells us that we have the potential to produce insulin from adult stem cells to help people with diabetes," said Dr. Randall J. Urban, senior author of the paper, professor and chair of internal medicine at the University of Texas Medical Branch at Galveston and director of UTMB’s Nelda C.
[1] Mitosis: division of the nucleus of any type of cell, separating the duplicated genome into two sets identical to the parent's. Stem cells replicate by mitosis.
[2] Differentiation: The process by which a cell acquires the characteristics and specialized function of a particular tissue type.
[3] Plasticity : the degree, varying in different types of stem cells, to which a stem cell is able to change into different tissue types.
[4] Progenitor cells are found in the various tissues of the body and can differentiate, but not renew themselves through dividing. Their main role is to replace cells lost by normal attrition.
[5] The information in this section is mostly taken from the website of the US National Institutes of Health, the US federal health research agency. http://stemcells.nih.gov/info/basics/basics1.asp
[6] Embryonic stem cells can also be isolated from cloned embryos. More information on so-called “therapeutic cloning” is included in the section on cloning.
[9] Information in this section has been taken from the website of the University of Utah, Genetic Science Learning Center http://gslc.genetics.utah.edu/units/stemcells/sctoday/
[10] The following examples have been taken from the archives of LifeSiteNews.com. Since the late 1990’s, LifeSiteNews.com has been recording countless instances of theraputic uses and experimental breakthroughs of adult stem cells, many of which were not reported or were underreported in the mainstream media. Vastly more information than can be recorded in this document is available at http://www.lifesite.net/ . Type the key words “adult stem cells” into the site’s search engine.
[18] http://www.lifesite.net/ldn/2007/may/07052809.html
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