Backgrounder—Stem Cell Research

INTRODUCTION

Stem cell research, continues to be an important, yet divisive, scientific and health policy issue for the country. The term “stem cell” generally means one of two types—embryonic stem cells or adult stem cells. The current controversy surrounds human embryonic stem cells. These cells are derived from fertilized embryos less than a week old that would otherwise be discarded by in vitro fertilization clinics if not donated to help other infertile couples or for research.

Embryonic stem cells are of great interest to medicine and science because they can develop into virtually any other cell made by the human body. In theory, if stem cells can be grown and their development directed in culture, it would be possible to grow cells of medical importance such as bone marrow, neural tissue, or muscle.

In contrast, adult stem cells are already specialized and their potential to regenerate damaged tissue is limited. For example, skin cells only become skin, and cartilage cells only become cartilage. Also, many vital organs in adults do not have stem cells.

In August 2001, President Bush announced his decision to restrict federal funding of stem cell research to stem cell lines that had already been created. A registry of such lines was set up at the National Institutes of Health (NIH). Scientists can work with those lines; they are not prohibited from conducting research on stem cell lines developed after that date as long as they do not use federal funding. Individual states are not prohibited from passing laws or adopting policy to support stem cell research using state funding. As a result, some states have acted to encourage such research within their borders. Scientists are also free to use private money for stem cell research.

The information that follows was derived primarily from NIH information and resources.

WHAT IS A STEM CELL?

A stem cell is a cell from an embryo, fetus, or adult that can, under certain conditions, reproduce itself for long periods or, in the case of adult stem cells, throughout the life of the organism. It also can give rise to specialized cells that make up the distinct tissues and organs of the body. All stem cells, regardless of their source, have three general properties—(1) they are capable of dividing and renewing themselves for long periods; (2) they are unspecialized; and (3) they can give rise to specialized cell types.

Scientists primarily work with two kinds of stem cells—embryonic stem cells and adult stem cells. Much of the basic understanding about embryonic stem cells has come from animal research. In the laboratory, an embryonic stem cell can proliferate indefinitely, a characteristic not shared by adult stem cells. In 1998, researchers discovered how to isolate stem cells from human embryos and grow them in the laboratory. These are called human embryonic stem cells (see below). The embryos used in these studies were created for infertility purposes though in vitro fertilization procedures and when no longer needed for such purposes, were donated for research with the informed consent of the donor.

WHAT CLASSES OF STEM CELLS ARE THERE?

There are three classes of stem cells: totipotent, multipotent, and pluripotent. A fertilized egg is considered totipotent, meaning that its potential is total; it gives rise to all the different types of cells in the body. Stem cells that can give rise to a small number of different cell types are generally called multipotent. And pluripotent stem cells can give rise to any type of cell in the body except those needed to develop a fetus.

WHAT ARE EMBRYONIC STEM CELLS?

Embryonic stem cells are unspecialized cells that can renew themselves for long periods and potentially grow into many, if not all, of the body’s tissues. They are derived from embryos that develop from eggs that have been fertilized in vitro (in a laboratory dish or test tube) in an in vitro fertilization clinic and that were then donated for research purposes with the informed consent of the donors. They are not derived from eggs fertilized in a woman’s body.

Embryonic stem cells serve as sort of a “repair system” for the body, theoretically able to divide without limit to replenish other cells for as long as the person or animal is still alive. When the cell divides, each “daughter” cell has the potential to remain either a stem cell or become another type of cell with a more specialized function, such as a muscle, a red blood, or a brain cell.

The embryos from which human embryonic stem cells are derived are typically four to five days old and are a hollow microscopic ball of cells called the blastocyst. The blastocyst has three structures (1) the trophoblast, which is the layer of cells surrounding the blastocyst; (2) the blastocoel, the hollow cavity inside the blastocyst; and (3) the inner cell mass, a group of approximately 30 cells at one end of the blastocoel.

HOW ARE EMBRYONIC STEM CELLS GROWN IN THE LABORATORY?

Growing cells in the laboratory is known as a cell culture. Human embryonic stem cells are isolated by extracting and transferring the inner cell mass into a plastic laboratory culture dish that contains a nutrient broth known as a culture medium. The cells divide and spread over the surface of the dish. Over the course of several days, the cells of the inner cell mass proliferate and begin to crowd the culture dish. When this happens, they are removed and plated into several fresh culture dishes. This process of replating the cells is repeated frequently over many months and is known as subculturing. After six months or more, the original 30 cells of the inner cell mass yield millions of embryonic stem cells.

Embryonic stem cells that (1) have proliferated in cell culture for six or more months without differentiating, (2) are pluripotent, and (3) appear genetically normal, are referred to as an embryonic stem cell line. (Differentiation is the process by which an unspecialized cell becomes specialized into one of the many that make up the body. )

Once stem cell lines are established, and even before that, batches can be frozen and shipped to other labs for further culture and experimentation. Once a stem cell line is established, it is essentially immortal, no matter how it is derived. The researcher using that line will not have to go through the procedure necessary to isolate stem cells again.

WHAT ARE ADULT STEM CELLS?

An adult stem cell is an undifferentiated (unspecialized) cell found among differentiated cells in a tissue or organ that can renew itself and differentiate to yield the specialized cell types of the tissue from which it originated. The primary role for adult stem cells in a living organism is to maintain and repair the tissue in which they are found. Adult stem cells are capable of making identical copies of themselves for the lifetime of the organism. (Some researchers use the term somatic stem cell instead of adult stem cell. )

Sources of adult stem cells include bone marrow, blood, the cornea and retina of the eye, brain, skeletal muscle, dental pulp, liver, skin, gastrointestinal tract lining, and pancreas. Most of the information about adult stem cells comes from studies of hematopoietic (blood-forming) stem cells isolated from the bone marrow and blood. Adult stem cells have been applied therapeutically for various diseases such as to restore various blood and immune components to the bone marrow via transplantation.

Adult stem cells uses are limited because (1) there is no isolated population of adult stem cells capable of forming all the kinds of cells in the body; (2) they are rare and often difficult to identify, isolate and purify; (3) insufficient numbers are available for transplantation; and (4) they do not replicate indefinitely in culture.

HOW DO EMBRYONIC AND ADULT STEM CELLS DIFFER?

Human embryonic stem cells are thought to have much greater developmental potential than adult stem cells. This means that embryonic stem cells may be pluripotent (able to give rise to cells found in all tissues of the embryo), rather than merely multipotent (restricted to specific cell types as adult stem cells are thought to be). Some evidence suggests that adult stem cell plasticity (the ability of an adult stem cell from one tissue to generate the specialized cell type of another tissue) may exist, increasing the number of cell types a given adult stem cell can become.

Large numbers of embryonic stem cells can be grown relatively easily in culture, while adult stem cells are rare in mature tissues. Large numbers of cells are needed for stem cell replacement therapies.

WHAT ARE THE POTENTIAL USES OF HUMAN STEM CELLS?

Although research is only in its early stages, scientists believe that stem cells have potential in many different areas of health and medical research. Studies of human embryonic stem cells may provide information on the complex events that occur during human development. A primary goal of stem cell research is identifying how undifferentiated stem cells become differentiated. Some of the most serious medical conditions, such as cancer and birth defects, are due to abnormal cell division and differentiation. More and better understanding of the genetic and molecular controls of these processes may provide information on how such diseases arise and offer new therapy options.

Possibly the most important potential application of stem cell research is the generation of cells and tissues that could be used for cell-based therapies. Currently, donated organs and tissues are used to replace ailing or destroyed tissue, but the need for such transplantable organs and tissues exceeds available supply. Stem cells, directed to differentiate into specific cell types, may offer the possibility of renewable sources of replacement cells and tissues to treat conditions such as Parkinson’s and Alzheimer’s diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.

Another area of stem cell research cited involves the development of transplantable pancreatic tissues that can treat diabetes. This includes ways to direct the specialization of stem cells to become pancreatic islet-like cells that produce insulin and could be used to control blood glucose levels.

Stem cells could also be used to test new drugs. New medications could be tested for safety on differentiated cells generated from human pluripotent cell lines. Other kinds of cell lines are already used in this manner; cancer cell lines are used to screen potential anti-tumor drugs.

HAVE HUMAN EMBRYONIC STEM CELLS BEEN USED SUCCESSFULLY TO TREAT ANY HUMAN DISEASES?

Human stem cell research is still in its very early stages. Scientists have only been able to do experiments with human embryonic stem cells only since 1998, when a group at the University of Wisconsin developed a technique to isolate and grow the cells. Federal funds to support such research have been available since the summer of 2001 when President Bush announced his decision on federal funding for stem cell research.

As noted above, adult stem cells such as blood forming stem cells in bone marrow (hematopoietic stem cells or HSCs) are currently the only type of stem cell commonly used to treat human diseases. Physicians have been transferring HSCs in bone marrow transplants for over 40 years. More advanced techniques of collecting or harvesting HSCs are now used to treat leukemia, lymphoma, and various inherited blood disorders.

WHAT IS THE FEDERAL POLICY ON STEM CELL RESEARCH?

On August 9, 2001, President Bush announced that federal funds may be awarded for research using human embryonic stem cells only if the following are met: (1) the cells’ derivation process (which begins with the embryo’s destruction) was initiated prior to 9 p. m. on that date; (2) the cells were derived from an embryo that was created for reproductive purposes and was no longer needed; and (3) informed consent was obtained for the donation of the embryo and the donation must not have involved financial inducements. No federal funds can be used, either directly or indirectly, to support research on human embryonic stem cell lines that do not meet the criteria established on August 9, 2001. The National Institutes of Health (NIH), the federal government’s leading biomedical research organization, is responsible for implementing the President’s policy.

As of the third quarter of 2004, 22 human embryonic stem cell lines were available for federally supported researchers. Information on the lines can be found on the NIH Stem Cell Registry.

While federal policy limits use of federal funds to create new embryonic stem cell lines, it does not bar scientists from using private or state money (see below).

MAY STATES PASS LAWS ON EMBRYONIC STEM CELL RESEARCH?

Individual states have the authority to pass laws allowing and promoting human embryonic stem cell research including using state funds. Unless the U. S. Congress passes a law that bans it, states may fund research using human embryonic stem cell lines that are not eligible for federal funding.

HAVE ANY STATES TAKEN ACTION ON STEM CELL RESEARCH?

California and New Jersey have enacted legislation and taken other actions in support of stem cell research. California passed a law in 2002 (SB 253, effective January 1, 2003) authorizing the use of stem cells for research. It requires the review of human stem cell research by an approved institutional review board. It also authorizes the donation of a human embryo pursuant to specific requirements and fund a dead body prohibits the purchase or sale of embryonic or cadaveric fetal tissue for research purposes (see OLR Report No. 2004-R-0081).

In November 2004, California voters approved a ballot initiative (“Proposition 71”) to create a $ 3 billion stem cell research fund that will use tax-free state bonds to provide about $ 295 million a year over 10 years to fund the research. This initiative creates the California Institute for Regenerative Medicine. The institute will make grants and loans for stem cell research, support all stages of the process, and establish appropriate regulatory standards and oversight bodies for research facilities and development.

The California controller will annually audit the institute’s finances. A citizen’s financial accountability oversight committee chaired by the controller will review the audit and institute’s financial practices. Proposition 71 also creates a 29-member independent citizen’s oversight committee, separate from the financial oversight committee, with full power and authority over the institute. This committee consists of representatives from University of California system campuses with medical schools, other California universities and research institutions, disease advocacy groups, and medical therapy development experts.

The California initiative gives funding priority to research that has the greatest potential for therapies and cures but cannot, or is unlikely to, receive federal funding. It prohibits use of bond money for funding of human reproductive cloning. (Another California law bans all human cloning in the state for reproductive purposes, i. e. , any effort to create a cloned individual. )

(For more information, see the California secretary of state’s website at http: //www. ss. ca. gov. )

New Jersey became the second state in the nation to authorize human embryonic stem cell research with passage of legislation that took effect in January 2004 (Chap. 203 of the N. J. public Laws of 2003). Like California, New Jersey requires review of stem cell research by an institutional review board and specifically outlaws human cloning.

In May 2004, Governor McGreevey announced the creation of a state-supported stem cell institute. The “Stem Cell Institute of New Jersey” is a joint research institute run by the University of Medicine and Dentistry of New Jersey and Rutgers University and funded through a public-private partnership (see OLR Reports Nos. 2004-R-0081 and 2004-R-0452).

WHERE CAN I GET MORE INFORMATION ON STEM CELL RESEARCH?

A detailed primer on stem cells can be found at http: //stemcells. nih. gov/info/basics.

For more information on the federal government’s policy on stem cell research, go to http: //stemcells. nih. gov/fedPolicy/NIHFedPolicy. asp.

For a listing of all the information about stem cells on the NIH web site go to http: //stemcells. nih. gov/.

A glossary of stem cell-related terms is found at http: //stemcells. nih. gov/info/glossary. asp.

A commercial, online newsletter featuring stories about stem cells of all types is located at http: //www. stemcellresearchnews. com/.

The University of Wisconsin has a web site about stem cells, written for general audiences, at http: //www. news. wisc. edu/packages/stemcells/.

A recent article about stem cell research at the University of Connecticut can be found at http: //www. dailycampus. com/global_user_elements/printpage. cfm?storyid=824916.

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