NIH Guidelines for Human Stem Cell Research FAQs

What organization should submit the "Request for Human Embryonic Stem Cell Line to be Approved for Use in NIH Funded Research"?

The submitting entity should have the authority and/or rights pertaining to the human embryonic stem cell line (e.g., be the owner, deriver or licensee or have written permission of the same to submit). If you are not sure whether your organization should submit a request, seek appropriate advice from within your organization, such as from your organization's legal counsel.

Who is the Signing Official in my organization?

The Signing Official should be an individual with direct or delegated authority to sign on behalf of the organization/submitting entity and verify that the information submitted on Form 2890 is correct. In some cases, this may be an individual who serves as a Signing Official for purposes of submitting grant applications to the NIH. Please note that there are Assurance, Certification, and Authority boxes in NIH Form 2890 that should be checked by the Signing Official if he/she is submitting the form. If you are not a Signing Official, do not check the boxes, but provide, as one of the attached supporting documents, a letter signed by the Signing Official that provides the required certifications (see the sample letter in Form 2890).

What materials should I consider including in my submission?

Relevant materials may include, for example, the consent for donation of embryos for research purposes, the consent for reproductive treatment (including the consent for cryopreservation of embryos, if applicable), and the research protocol or other document(s) demonstrating the relative timing of reproductive treatment and the donation of embryos for research purposes. The materials must be those that were in effect at the time of the embryo donation.

I am a scientist funded by the NIH. How many cell lines are available to me, and how do I get them?

Who owns the cells?

The stem cell lines remain the property of the individual stem cell providers, as listed on the NIH Human Embryonic Stem Cell Registry. Researchers may negotiate a material transfer agreement (MTA) with the cell providers in order to specify their rights and responsibilities concerning resulting data, publications, and potential patents.

What types of stem cell research are governed by the NIH Guidelines for Human Stem Cell Research?

Are there any restrictions on the use of lines listed on the NIH Human Embryonic Stem Cell Registry?

The "see details" link on the NIH Human Embryonic Stem Cell Registry includes information on two categories of possible use restrictions: Provider Restrictions and NIH Restrictions. Provider Restrictions include things such as experiments that are prohibited with the cell line, or requirements that proposed research be approved by an ESCRO or other type of ethical review committee. NIH Restrictions are imposed on the use of a line based on the usage of the cells as agreed to by the donors in their informed consent process. Furthermore, other cell lines derived from a restricted hESC line are subject to the same restriction.

Once a human embryonic stem cell line is listed on the NIH Human Embryonic Stem Cell Registry, are lines derived from it also eligible?

The NIH Guidelines on Human Stem Cell Research focus on the requirements for donation of the embryo that was used for derivation. Once that determination has been made for a particular line, it applies to all subclones or modifications. For example, now that WA01 (H1) is eligible for NIH funding, WA01 lines that express GFP are also eligible.

Should scientists list the name of the subclone in their NIH grant application?

Yes, scientists should refer to the parent hESC line and list the cell line name of the modified line or subclone in the research plan of their application.

Can a scientist use federal funds to conduct research using derivatives of human embryonic stem cell lines that are not listed on the NIH Human Embryonic Stem Cell Registry?

No federal funds may be used, either by an awardee or a sub-recipient, to support research using derivatives of human embryonic stem cell lines (hESCs) that are not listed on the NIH Human Embryonic Stem Cell Registry, with the exception described below. Derivatives include, but are not limited to, subclones of hESC lines, modified hESC lines (such as a line expressing green fluorescent protein), differentiated cells developed from hESC lines (such as muscle progenitor cells), and cellular materials (such as DNA, RNA, and proteins). Thus, no federal funds may be used for the generation of new data from unapproved hESC lines or derivatives. However, publicly accessible data from unapproved lines or derivatives may be used and analyzed with federal funds.

Can genomic data generated from human embryonic stem cells (hESCs) not listed in the NIH Human Embryonic Stem Cell Registry be submitted to an NIH-designated data repository (e.g., database of Genotypes and Phenotypes (dbGaP)) under the Genomic Data Sharing (GDS) Policy?

No, genomic data generated from hESCs that are not listed on the NIH Human Embryonic Stem Cell Registry will not be accepted by NIH-designated data repositories such as dbGaP.

Does the NIH require that hESC lines on the NIH Human Embryonic Stem Cell Registry meet the FDA 'Donor Eligibility Rule' (21 CFR 1271 Part C) requirements?

No. The NIH does not require that lines listed on the Registry meet the FDA requirements of 21 CFR 1271 Part C. To be listed on the NIH Human Embryonic Stem Cell Registry, lines must meet the NIH Guidelines for Human Stem Cell Research, which focus on ethical requirements pertaining to the embryo donation process. Thus, the embryo donor screening and testing requirements for relevant communicable diseases agents or diseases in 21 CFR 1271 Part C are not incorporated in the NIH Guidelines. Researchers interested in developing a clinical product, which would be regulated by the FDA, should contact the FDA for more information, ideally prior to donation of the embryo.

See: Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products.

Are the documents related to the hESC lines listed on NIH hESC Registry available to the public?

Do universities (or other non-Federal entities) need to maintain separate labs for conducting research with hESC lines that do not meet the NIH Guidelines?

NIH does not require universities to maintain separate labs for ineligible hESC research, but only requires that the costs be segregated properly, using the same principles as apply to other research supported by both NIH and other sources of funding. Some institutions chose to address the segregation of costs issue by creating separate facilities. Long standing accounting requirements for Federal projects provided in Federal cost principles (implemented by HHS at 45 C.F.R. Part 75, Subpart E)) assure that costs charged to Federal projects do not improperly subsidize non-Federal research.

Can universities (or other non-Federal entities) allow equipment that was purchased with NIH funds to be used on non-federally supported projects?

Yes, consistent with Federal law (Federal Grant and Cooperative Agreement Act, 31 U.S.C. 6306) and Federal regulation (45 C.F.R. 75.319(c); 45 C.F.R. 75.320), universities can allow equipment that was purchased with NIH funds for Federally-supported research projects to be used on non-Federally supported projects, in addition to the original purpose(s) in furtherance of the grant activities.

How does the requirement regarding the right to withdraw consent for embryo donation in the Guidelines compare to that in the Common Rule?

Section IIA of the NIH Guidelines for Human Stem Cell Research requires that “Donor(s) should have been informed that they retained the right to withdraw consent until the embryos were actually used to derive embryonic stem cells or until information that could identify the donor(s) was no longer retained by the researchers, if applicable.” The Federal Policy for the Protection of Human Subjects Subpart A ('Common Rule') §46.116 requires "A statement that…the subject may discontinue participation at any time…"

The Guidelines reflect that the time for embryo donors to withdraw consent for use of the embryos is limited to the period before embryonic stem cells are derived.

For projects studying human germ cells and/or gametes in animal models: how could an institution demonstrate that it will be in compliance with Section IV.B. of the NIH Guidelines for Human Stem Cell Research (no research involving the breeding of animals where the introduction of hESCs or hiPSCS may contribute to the germ line)?

What exactly do the current Guidelines say and what are you proposing to change?

Why has the NIH proposed to revise the Guidelines?

The NIH learned from the scientific community that there are scientifically important sources of human embryonic stem cells (hESCs) that may otherwise meet the strict ethical requirements of the Guidelines, but do not meet the precise definition of hESCs in the current Guidelines. The NIH is proposing to make a technical change to the wording of the Guidelines so that they can consider the eligibility of hESCs that have been derived earlier in the development of the embryo. This change would not allow for lines that are derived from embryos that have developed beyond the blastocyst stage. It is important to note that the proposed change to the definition would not alter the rigorous ethical standards in the Guidelines for donation of embryos for hESC research.

Is the NIH proposing to revise other aspects of the Guidelines?

No. The NIH is only proposing this technical change to the definition of hESCs. At some point in the future, the NIH may consider the other changes to the Guidelines, per the Executive Order from President Obama.

Why were three hESC lines from Children's Hospital Boston on the Registry put "on hold"?

When the NIH was asked by a deriver to consider the eligibility of hESCs that do not meet the current definition, the Agency realized that it had inadvertently listed several lines on the Registry that were derived from early stage embryos that had not reached the blastocyst stage. These three lines are on “hold” and should not be used in NIH-funded research until the NIH reviews the public comments on the proposed change to the Guidelines and makes a final decision about a change in the definition of hESCs. At that time, depending on the outcome of the proposed change to the Guidelines, the NIH will either take the lines off “hold” status so that they can be used in NIH-funded research or remove them from the Registry. It is important to note that these lines met all of the ethical requirements under the Guidelines.

Does NIH have a mechanism to consider whether research proposals involving human embryos can be supported by NIH?

Yes. The NIH Human Embryo Research Steering Committee determines whether particular proposed research is supportable by NIH given the limitations detailed in the NIH Grants Policy Statement Sec. 4.2.4 (for extramural research; the same limitations apply to NIH intramural research). The Steering Committee is composed of NIH staff with expertise in reproductive biology, law, policy, and NIH processes to review research proposals. Questions can be sent to the attention of this Steering Committee through the following email: [email protected].

Can NIH-supported researchers create or use human stem cells that have the ability to develop into all embryonic and extra-embryonic cell types?

If the cells could be considered an organism, as described in the NIH Grants Policy Statement Section 4.2.4, then such research is subject to the limitations described in Section 4.2.4. Note that NIH considers a human totipotent cell to be an organism under NIH Grants Policy Statement Section 4.2.4.

Will NIH support research to create or use models of human embryos, sometimes referred to as "human embryoids"?

NIH will not support research with a model that could be considered a human organism per the NIH Grants Policy Statement Section 4.2.4. NIH considers the characteristics of the specific model; see Sharing Our Current Thinking: Models Containing Aspects of Human Embryos. While NIH continues to make decisions on a case-by-case basis, the research community should be aware that NIH has supported research with some human 2-dimensional micropattern cultures. NIH has also decided that the agency may not support research with some human blastula-stage models composed of epiblast and extra-embryonic cells in a relatively normal spatial orientation.

May individual states pass laws to permit human embryonic stem cell research?

Yes, individual states have the authority to pass laws to permit human embryonic stem cell research using state funds.

Where can I find information about patents obtained for stem cells?

The U.S. Patent and Trademark Office offers a search feature for issued patents and published applications.

The NIH Guidelines for Research Using Human Pluripotent Stem Cells, published on August 25, 2000, contained guidance regarding the Utilization of Human Pluripotent Stem Cells Derived from Human Fetal Tissue (Section IIB). Does this guidance still govern NIH-funded research with human pluripotent stem cells derived from human fetal tissue?

NIH interprets the NIH Guidelines for Human Stem Cell Research, effective on July 7, 2009, as superseding the 2000 NIH Guidelines for Research Using Human Pluripotent Stem Cells. As stated in the 2009 Guidelines, “these Guidelines implement Executive Order 13505, as it pertains to extramural NIH-funded stem cell research, [and] establish policy and procedures under which the NIH will fund such research…” It was NIH’s intent to have the 2009 Guidelines address all NIH stem cell research, therefore Section IIB of the 2000 NIH Guidelines for Research Using Human Pluripotent Stem Cells is no longer in effect.

The 2009 NIH Guidelines for Human Stem Cell Research focus primarily on pluripotent stem cells derived from human embryos. Is there NIH policy that applies to research using human fetal tissue?