With the promise of powerful new treatments—and even cures—for disabling and deadly diseases, today’s scientific stem-cell gold rush is surging. Despite controversy and regulations regarding the ethics of stem-cell research, companies and universities worldwide have patented 3,000 discoveries using stem-cell techniques over the past five years, according to the Biotechnology Report 2005.
What once seemed unimaginable now appears at least possible as stem-cell scientists develop new tools that could lead to reversing the course of Alzheimer’s, Parkinson's, heart disease, spinal cord injuries, cancers and other critical conditions.
The object of intense investigation: the embryonic stem cell, i.e. a single cell derived from the 100 or so human cells which make up a pinhead-sized five to seven day old embryo called a blastocyst. Embryonic stem cells are capable of becoming any one of the nearly 220 different cell types in our adult bodies, from heart to brain. Stem cells were so named because every cell in the body “stems” from these self-replicating cells.
Since most specialized cells don’t replace themselves after serious damage or disease, embryonic stem cells contain the promise of replacing dysfunctional cells with new healthy cells.
All of us have small numbers of “adult stem cells” in our bodies. These cells facilitate growth and repair in the organs such as bone marrow, skin, and gut which do undergo growth, replacement, or repair. However, in contrast to embryonic stem cells, adult stem cells are scarcer and less versatile than their embryonic precursors. Found in many tissues and organs, including blood, brain, and bone marrow, adult stem cells haven’t yet proved they can morph into every kind of cell. This is in contrast to early-embryonic stem cells, which so far seem able to take on any adult cell form. Within their known limits, adult stem cells have been used to treat a variety of conditions, including blood diseases like sickle-cell anemia.
Stem cell research has exploded since 1998, when the University of Wisconsin’s Dr. James Thomson discovered how to isolate stem cells from human embryos and “harvest” the cells in a laboratory.
To study embryonic stem cells, scientists typically obtain week-old frozen embryos (blastocysts) from fertility clinics. Because most infertile couples seek implantation with an embryo that is genetically related to them, embryos that remain frozen after couples decide not to seek additional pregnancies are routinely destroyed. Some of these embryos were used by Dr. Thomson and others to create embryonic stem cells lines through the process described below.
Some 30 microscopic stem cells extracted from the inner cell mass of the blastocyst are transferred to a nutrient-rich laboratory culture dish lined with a layer of mouse embryonic skin cells known as a feeder layer. This layer provides a sticky surface to which stem cells attach. (Since mouse cells might be able to transfer potentially harmful viruses to humans, researchers recently began investigating how to grow cells without mouse feeder cells.)
When stem cell colonies outgrow their culture dishes—generally within several days—they are divided and transferred into fresh culture dishes. This process can theoretically be repeated indefinitely, producing millions of embryonic stem cells grown from an original batch of 30 cells. When these cells continue dividing into identical cells for six months or more, they are deemed pluripotent—which means they have the capacity to develop into any type of cell in the body.
A stem cell line is a mass of cells descended from one original early-stage embryonic stem cell having its origins in a week-old human blastocyst. Every cell in this “line” shares the original cell’s genetic characteristics. Batches of cells can be separated from a cell line and distributed to researchers who work at customizing or “engineering” these cells for transplantation or treatment of diseases. Once established , a stem cell line will continue dividing indefinitely in the laboratory and as a result is often termed “immortal”.
Once stem cell lines are created, customization requires that these cells be induced to undergo differentiation. Differentiation is the process by which an unspecialized early-embryonic cell acquires the features of a specialized cell such as a heart, liver, or muscle cell. The process may include tinkering with the chemical composition of the culture medium, altering the culture dish’s surface, or modifying cells by inserting specific genes. While the task of harvesting embryonic stem cells in a stable replicating colony is complex, guiding embryonic cell differentiation is even more daunting.
In order to be useful stem cells must be differentiated into cell types such as heart, liver, muscle, or brain. However, in order to be effective in patients they must also be genetically matched to the individuals who may someday receive them. If cells are not matched they risk being destroyed by the body's immune system. In the May 20, 2005 issue of the journal Science , Seoul National University researcher Hwang Woo-suk reported a stunning step forward for stem cell science, detailing a new technique for cloning embryonic stem cells that are genetically matched to people diagnosed with specific diseases.
Known as somatic cell nuclear transfer, the process involves taking an egg (donated by someone completely unrelated to the patient who would receive treatment) and removing it’s gene-containing nucleus. Then, DNA from the patient (the Seoul researchers used tiny snips of skin as a source) is put into the egg. Next, the researchers jump-started cellular division with chemicals, fueling successful growth of 31 blastocysts. Scientists went on to harvested 11 colonies, or lines of stem cells, that genetically matched cells of the 11 patients who had donated a skin snippet.
Cloning customized stem cells from injured or ill patients is being hailed by stem cell specialists as an enormous advance towards replacing organs and tissue to treat diseases. It is important to recognize, however, that this process allowed scientists to make cells that might survive and grow in the body of a sick or injured person, but whether such customized stem cells can repair diseased or injured tissues still remains unproven.
Amid expectations for a new era of regenerative medicine, embryonic stem cell science is still in its infancy, with treatments predicated to be years away. While U.S. stem-cell scientists are hampered by federal-funding restrictions, embryonic stem cell therapy may surface sooner in more lenient regions like Europe’s United Kingdom, which developed the world’s first stem cell bank last year. Eventually, experts predict custom-made tissues and organs could be created through a combination of stem cells, cloning and genetic engineering.
RESOURCES:
American Parkinson Disease Association
http://www.apdaparkinson.com/
Juvenile Diabetes Research Foundation International
http://www.jdrf.org/
National Spinal Cord Injury Association
http://www.spinalcord.org/
References:
Aguilera-Hellweg M. The Power to Divide. National Geographic . July 2005; 3-27.
Clive C. The Mother of All Cells. Scientific American . 2005; 293; 0036:A6
International Society for Stem Cell Research. Available at: http://www.isscr.org/ . Accessed July 2005.
National Institutes of Health. Available at: http://stemcells.nih.gov/info/basics/ . Accessed July 2005.
Last reviewed July 2005 by Lawrence Frisch, MD, MPH
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