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Stem Cells: Scientific Progress and Future Research Directions

Government document

By: Ruth L. Kirchstein

By: Lana Skirboll

Date: 2001

Source: R. L. Kirchstein and L. Skirboll. Stem Cells: Scientific Progress and Future Research Directions. Washington, D.C.: U.S. Department of Health and Human Services, 2001. Available online at 〈〉 (accessed August 20, 2005).

About the Author: Ruth Kirchstein is a former acting director of the National Institutes of Health (NIH). She obtained her Doctor of Medicine degree at Tulane University School of Medicine in 1951. Subsequently she worked as a researcher in experimental pathology at the Division of Biologics Standards. Following the change of the division to a bureau of the Food and Drug Administration in 1972, she became a deputy director. In 1974, she became the first woman institute director at the NIH. One of her achievements relates to the promotion of the Sabine polio vaccine. She was also involved in the AIDS campaign at the beginning of the epidemic. Lana Skirboll is the director of Office of Science Policy at the NIH. She advises the NIH director and the NIH institutes on the policies and procedures for safe conduct of biological research. Among other activities, she is also responsible for development of the NIH's guidelines for research using human stem cells.


The National Institutes of Health (NIH) are a part of the U.S. Department of Health and Human Services. The NIH, which is comprised of twenty-seven institutes and centers in the United States, conduct and support medical research in this country and in other parts of the world.

The NIH have compiled information on stem cells themselves, the areas in which they are used, and protocols used for obtaining, growing, manipulating, and transplanting them. All research on stem cells performed in any of the institutes of the NIH or any other federal institution must comply with the Federal Stem Cell Policy.

Federally funded research on human embryonic stem cells only can be performed on the cell lines that are in the NIH stem cell registry. Other cell lines can be submitted to the registry provided that they fulfill the eligibility criteria. The most important criterion is that the process of removal of cells from the embryo must have been initiated before August 9, 2001. The other criteria are: 1) the stem cells were obtained from an embryo generated for reproductive purposes that is no longer needed for that purpose; 2) an informed consent was obtained from the donor; 3) the donor received no financial compensation for the donation.

All of the cell lines in the cell registry are accompanied by a detailed description of the markers, karyotype, passage, and conditions used for growing, thus providing the potential researcher with all of the important information needed for their use. Currently a limited number of lines is available due to an on-going derivation process, and also due to the fact that some of the cell lines initially registered are unusable because they have failed to expand into undifferentiated cells.

While mouse embryonic stem cells have been used in research since 1981, the first human embryonic stem cells were isolated and grown in culture in 1998 by James Thomson at the University of Wisconsin. Research on the mouse stem cells has revealed the ways in which their development can be manipulated to form cells of various tissues. It was discovered that, under the appropriate conditions, these stem cells could form any cell type found in the body, such as neurons, blood, muscle, or bone cells. Therefore, embryonic stem cells are considered pluripotent, meaning that they are able to generate any tissue and cell type in the body.

Subsequent studies in adult animals and humans showed the presence of stem cells in adult tissues. The most commonly isolated adult stem cells are the hematopoietic stem cells. However, the numbers of stem cells in adult tissues are much lower than in embryonic tissues and generally they are more limited in the types of cells they can form. Yet, adult stem cells still exhibit some level of plasticity—the ability to differentiate into cells of different tissue types.

Researchers believe that embryonic stem cells may be of particular use in the treatment of neurological diseases, such as Parkinson's disease or Alzheimer's disease. These stem cells also may be useful for research in regeneration of damaged nerves, heart muscle, and other tissues. Another emerging area of study involves the use of the stem cells in combination with gene therapy. The ease of manipulation of embryonic stem cells may be important for delivering targeted gene therapy.

In the search for human embryonic stem cells, the stocks of unimplanted embryos in fertility clinics became a target for researchers who wanted to generate lines of these cells for use in future treatments. However, the use of these embryos quickly raised ethical and legal questions. Moreover, a number of practical and safety issues relating to the use of such cells also emerged.

The NIH report on stem cells was compiled at the request of the Secretary of Health and Human Services, T. G. Thompson. It provides basic information about stem cells derived from all possible sources—embryonic tissues, fetal tissues, and adult tissues. This report was written in such a way that it is useful both to the general public and to scientists. It includes general information about stem cells, their derivation, and their possible applications in the treatment of a number of diseases. However, it makes no recommendations regarding the research on stem cells. The report also does not address the legal and ethical issues involved in the use of stem cells for research.


A stem cell is a cell that has the ability to divide (self replicate) for indefinite periods—often throughout the life of the organism. Under the right conditions, or given the right signals, stem cells can give rise (differentiate) to the many different cell types that make up the organism. That is, stem cells have the potential to develop into mature cells that have characteristic shapes and specialized functions, such as heart cells, skin cells, or nerve cells….

Most scientists use the term pluripotent to describe stem cells that can give rise to cells derived from all three embryonic germ layers—mesoderm, endoderm, and ectoderm. These three germ layers are the embryonic source of all cells of the body….

Unipotent stem cell, a term that is usually applied to a cell in adult organisms, means that the cells in question are capable of differentiating along only one lineage….

The embryonic stem cell is defined by its origin—that is from one of the earliest stages of the development of the embryo, called the blastocyst…. The embryonic stem cell can self-replicate and is pluripotent—it can give rise to cells derived from all three germ layers.

The adult stem cell is an undifferentiated (unspecialized) cell that is found in a differentiated (specialized) tissue; it can renew itself and become specialized to yield all of the specialized cell types of the tissue from which it originated. Adult stem cells are capable of self-renewal for the lifetime of the organism. Sources of adult stem cells have been found in the bone marrow, blood stream, cornea and retina of the eye, the dental pulp of the tooth, liver, skin, gastrointestinal tract, and pancreas….

A hematopoietic stem cell is a cell isolated from the blood or bone marrow that can renew itself, can differentiate to a variety of specialized cells, can mobilize out of the bone marrow into circulating blood, and can undergo programmed cell death, called apoptosis….

Ultimately, stem cell gene therapy should allow the development of novel methods for immune modulation in autoimmune diseases. One example is the genetic modification of hematopoietic stem cells or differentiated tissue cells with a "decoy" receptor for the inflammatory cytokine interferon gamma to treat lupus. For example, in a lupus mouse model, gene transfer of the decoy receptor, via DNA injection, arrested disease progression….

Efforts to develop stem cell based therapies for Parkinson's Disease provide a good example of research aimed at rebuilding the central nervous system. As is the case with other disorders, both the cell-implantation and the trophic-factor strategies are under active development. Both approaches are promising. This is especially true of cell implantation, which involves using primary tissue transplanted directly form developing fetal brain tissue….

The partial repair of the damaged heart muscle suggests that the transplanted mouse hematopoietic stem cells responded to signals in the environment near the injured myocardium. The cells migrated to the damaged region of the ventricle, where they multiplied and became "specialized" cells that appeared to be cardiomyocytes….

Transplanted human stem cells are dynamic biological entities that interact intimately with—and are influenced by—the physiology of the recipient. Before being transplanted, cultured human stem cells are maintained under conditions that promote either the self-renewing expansion of undifferentiated progenitors or the acquisition of differentiated properties indicative of the phenotype the cells will assume. After incompletely differentiated human stem cells are transplanted, additional fine-tuning occurs as a consequence of instructions received from the cells' physiologic microenvironments within the recipient.

Assessing human stem cell safety requires the implementation of a comprehensive strategy. Each step in the human stem cell development process must be carefully scrutinized. Included in this global assessment are the derivation, expansion, manipulation, and characterization of human stem cell lines, as well as preclinical efficacy and toxicity testing in appropriate animal models. Being able to trace back from the cell population prepared for transplantation to the source of the founder human stem cells also allows each safety checkpoint to be connected, one to the other….

In addition, hematopoietic stem cells "home," or migrate, to a number of different spots in the body—primarily the bone marrow, but also the liver, spleen, and lymph nodes. These may be strategic locations for localized delivery of therapeutic agents for disorders unrelated to the blood system, such as liver diseases and metabolic disorders such as Gaucher's disease….


The ability to use stem cells in disease treatments by simple transplantation makes them a feasible therapeutic approach. It is possible to use a patient's own stem cells for treatment or to utilize a line of embryonic stem cells that have been isolated from other individuals and stored.

In the majority of current and possible future treatments, stem cells are differentiated in the laboratory to generate cells similar to those that are intended for replacement. These manipulated cells are then transplanted into the patient's target organs. It is essential to standardize the methods for isolation, manipulation, and transplantation of the cells to ensure patient safety.

Screening for antigens (foreign substance that can induce an immune response) is one of the most important issues confronting the therapeutic use of stem cells. (Such screening is routinely done in traditional organ transplantation procedures.) In addition, the cells must be examined for pathogens (disease-causing organisms) to ensure that the patient is not given an infectious disease along with the stem cells.

Hematopoietic stem cells already have been used in treating leukemias, and are part of a reasonably well established and accepted method of treatment. They are the only stem cells currently used to treat diseases.

The use of other stem cells, especially human embryonic stem cells, is under development. There are three main areas that require further study. The first area concerns the development of methodologies to differentiate the stem cells into the cells required in a particular tissue. The second research area involves the development of a system or systems to deliver the cells into the tissues. Finally, ways to prevent the rejection of stem cells by the recipient also require more study.

With a limited supply of organs for transplants, stem cells are increasingly viewed as an attractive alternative for treating failing organs. However, much more research is needed and clinical trials are essential before human embryonic stem cells become a viable and accepted treatment.



Thomson, Alison, and Jim McWhir, eds. Gene Targeting and Embryonic Stem Cells (Advanced Methods). Oxford: BIOS Scientific Publishers, 2004.


Kaufman, D. S., and J. A. Thomson. "Human ES Cells—Haematopoiesis and Transplantation Strategies." Journal of Anatomy 200 (2002): 243-248.

Li, X., et al. "Specification of Motoneurons From Human Embryonic Stem Cells." Nature Biotechnology 23 (2005): 215-221.

Prelle, K., N. Zink, and E. Wolf. "Pluripotent Stem Cells—Model of Embryonic Development, Tool for Gene Targeting, and Basis of Cell Therapy." Anatomia, Histologia, Embryologia 31 (2002): 169-186.

Thomson, J. A., et al. "Embryonic Stem Cell Lines Derived From Human Blastocysts." Science no. 5391 (1998): 1145-1147.

Yoon, Y., et al. "Clonally Expanded Novel Multipotent Stem Cells From Human Bone Marrow Regenerate Myocardium After Myocardial Infarction." Journal of Clinical Investigation 115 (2005): 326-338.

Web sites

The National Institutes of Health. "Stem Cell Information." 〈〉 (accessed June 15, 2005).

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Stem Cells: Scientific Progress and Future Research Directions

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