NIH Fact Sheet on Human Pluripotent Stem Cell Research Guidelines
Updated January 2001
The Promise of Stem Cell Research
Human pluripotent stem cells are a unique scientific and medical resource. In 1998, scientists at the University of Wisconsin and at Johns Hopkins University isolated and successfully cultured human pluripotent stem cells. The pluripotent stem cells were derived using non-Federal funds from early-stage embryos donated voluntarily by couples undergoing fertility treatment in an in vitro fertilization (IVF) clinic or from non-living fetuses obtained from terminated first trimester pregnancies. Informed consent was obtained from the donors in both cases. Women voluntarily donating fetal tissue for research did so only after making the decision to terminate the pregnancy.
Because pluripotent stem cells give rise to almost all of the cells types of the body, such as muscle, nerve, heart, and blood, they hold great promise for both research and health care. This advance in human biology continues to generate enthusiasm among scientists, patients suffering from a broad range of diseases, including cancer, heart disease and diabetes, and their families. For example, further research using human pluripotent stem cells may help:
- Generate cells and tissue for transplantation. Pluripotent stem cells have the potential to develop into specialized cells that could be used as replacement cells and tissues to treat many diseases and conditions, including Parkinson's disease, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.
- Improve our understanding of the complex events that occur during normal human development and also help us understand what causes birth defects and cancer.
- Change the way we develop drugs and test them for safety. Rather than evaluating the safety of candidate drugs in an animal model, drugs might be initially tested on cells developed from pluripotent stem cells and only the safest candidate drugs would advance to animal and then human testing.
The Potential of Adult Stem Cell Research
Questions have been raised about the usefulness of adult stem cells in research and treatment, especially as compared to pluripotent stem cells derived from embryos or fetal tissue. Indeed, there is enormous potential for research using such cells. Human adult stem cells have been isolated from tissues such as blood, brain, intestine, skin, and muscle. Furthermore, some adult stem cells have been shown to be more "plastic" than first thought—that is, some of these stem cells appear to be capable of developing into different kinds of cells than first predicted.
There is, however, considerable evidence that adult stem cells may have limited potential compared to pluripotent stem cells derived from embryos or fetal tissue. Human adult stem cells have not yet been isolated from all cell and tissue types, and they have not been shown to be capable of developing into all of the different cell and tissue types of the body. Furthermore, adult stem cells are difficult to obtain, since they are often present in only minute quantities. They are difficult to isolate and purify, and their numbers appear to decrease with age. Moreover, adult stem cells may have more DNA damage, and they appear to have a shorter life span than pluripotent stem cells. For all of these reasons, and because of the enormous potential of stem cell approaches to research and treatment, it is vitally important that scientists study and compare both pluripotent and adult stem cells.
The Need for Guidelines to Govern Research Using Pluripotent Stem Cells
The NIH is prohibited from using any appropriated funds for "... (1) the creation of a human embryo or embryos for research purposes; or (2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under 45 CFR 46.208(a)(2) and section 498(b) of the Public Health Service Act (42 U.S.C. 289g(b))." Because of the enormous potential of human pluripotent stem cells to medical research, the NIH asked the General Counsel of the Department of Health and Human Services (DHHS) to determine whether research utilizing pluripotent stem cells is permissible under existing Federal law governing embryo and fetal tissue research. After careful consideration, the DHHS concluded that because human pluripotent cells are not embryos, current Federal law does not prohibit DHHS funds from being used for research utilizing these cells.
Recognizing the ethical and legal issues surrounding human pluripotent stem cell research and the need for stringent oversight of this class of research—oversight that goes beyond the traditional rigorous NIH scientific peer review process—the NIH issued a moratorium on the funding of this research until Guidelines could be developed and an oversight process could be implemented.
In April 1999, the NIH convened a working group of the Advisory Committee to the Director (ACD), NIH, to provide advice to the ACD relevant to guidelines and oversight for this research. The working group met in public session and included scientists, clinicians, ethicists, lawyers, patients, and patient advocates. During their deliberations, the group considered advice from the National Bioethics Commission, the public, and scientists. Draft guidelines for this research were published for public comment, and, after reviewing and considering all comments received, the NIH Guidelines for Research Using Human Pluripotent Stem Cells (NIH Guidelines) were published in the Federal Register and became effective on August 25, 2000. (Because the NIH Guidelines contained a few incorrect citations and other minor errors, a notice of correction (65 FR 69951) was published on November 21, 2000.) The revised NIH Guidelines and other information about stem cell research can be found at the URL: http://stemcells.nih.gov/info/news.asp.
Specifics of the Guidelines
The purpose of the NIH Guidelines is to set forth procedures to help ensure that NIH-funded research in this area is conducted in an ethical and legal manner. By issuing these Guidelines, the NIH aims to enhance both the scientific and ethical oversight of this important arena of research and the pace at which scientists can explore its many promises. These Guidelines will encourage openness, provide appropriate Federal oversight, help make certain that all researchers can make use of these critical research tools, and help assure full public access to the practical medical benefits of research using these cells.
The Guidelines prescribe the documentation and assurances that must accompany requests for NIH funding for research using human pluripotent stem cells derived from human embryos or fetal tissue. These include the following:
- For studies using human pluripotent stem cells derived from human embryos, NIH funds may be used only if the cells were derived from frozen embryos that were created for the purposes of fertility treatment, were in excess of clinical need, and were obtained after the consent of the donating couple.
- The NIH Guidelines prohibit the use of inducements, monetary or otherwise, for the donation of the embryo. There must also have been a clear separation between the fertility treatment and the decision to donate embryos for this research.
- The NIH Guidelines require that the informed consent specify whether or not information that could identify the donor(s) will be retained.
- Investigators who propose using NIH funds to conduct research using human pluripotent stem cells derived from fetal tissue are expected to follow both the NIH Guidelines and all Federal and state laws and regulations governing human fetal tissue and human fetal tissue transplantation research.
- The Guidelines require that the donation of human embryos or fetal tissue be made without any restriction or direction regarding the individual(s) who may be the recipient of the cells derived from the human pluripotent stem cells.
- They also require review and approval of the derivation protocol by an Institutional Review Board.
- The informed consent should include statements that the embryos or fetal tissue will be used to derive human pluripotent stem cells for research that may include human transplantation research; that derived cells may be kept for many years; that the research is not intended to provide direct medical benefit to the donor; and that the donated embryos will not be transferred to a woman's uterus and will not survive the stem cell derivation process.
- The informed consent must also state the possibility that the results of the research may have commercial potential, and that the donor will not receive any benefits from any such future commercial development.
- The Guidelines also set forth the areas of research that are ineligible for NIH funding, including: 1) as required by law, research involving the derivation of pluripotent stem cells from human embryos; 2) research in which human pluripotent stem cells are utilized to create or contribute to a human embryo; 3) research utilizing pluripotent stem cells that were derived from human embryos created for research purposes; 4) research in which human pluripotent stem cells are derived using somatic cell nuclear transfer; 5) research utilizing human pluripotent stem cells that were derived using somatic cell nuclear transfer; 6) research in which human pluripotent stem cells are combined with an animal embryo; and 7) research in which human pluripotent stem cells are derived using somatic cell nuclear transfer for the purposes of reproductive cloning of a human.
Requirements for Investigators Applying for Funds
With the issuing of the Guidelines, the moratorium was lifted, and NIH is accepting applications for this class of research. A request for NIH funds for research using these cells must include a signed assurance that the cells were derived from human embryos or fetal tissue in accordance with the Guidelines and that the institution will maintain documentation in support of the assurance.
This assurance must also affirm that the human pluripotent stem cells to be used in the research were obtained through a donation or through a payment that does not exceed the reasonable costs associated with the quality control, processing, transportation, preservation, and storage of the stem cells. It must state that the proposed research is not a class of research that is ineligible for NIH funding.
Investigators must also submit a sample informed consent document, with patient identifier information removed, and a description of the informed consent process along with documentation of IRB approval of the derivation protocol. They must also provide an abstract of the scientific protocol used to derive human pluripotent stem cells along with a title of the research proposal that proposes the use of human pluripotent stem cells.
Ensuring Compliance with the Guidelines
Investigators requesting NIH funds for research using pluripotent stem cells will need to provide documentation that they are in compliance with the Guidelines prior to receiving NIH funds for this class of research. Submitted documentation will be reviewed by a newly-created NIH working group called the Human Pluripotent Stem Cell Review Group (HPSCRG).
Members of the working group will review documentation of compliance with the Guidelines for funding requests that propose the use of human pluripotent stem cells. They will also advise the NIH Center for Scientific Review Advisory Committee (CSRAC) of the outcome of their review, which, if appropriate, will be approved by the CSRAC. This decision will be forwarded to the funding Institute or Center. The HPSCRG will also hold public meetings when a request proposes the use of a line of human pluripotent stem cells that has not been previously reviewed by the HPSCRG.
The NIH is in the process of finalizing the members of the HPSCRG in preparation for a March deadline for the receipt of requests for NIH funding for human pluripotent stem cell research. The Agency has not, to date, received any applications for this class of research. In no event will NIH fund research or allow existing funds to be used for research using human pluripotent stem cells derived from human embryos or human fetal tissue until the derivation protocol has received HPSCRG review and CSRAC approval. Continued compliance with the Guidelines is a term and condition of the NIH award.
