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 an investigator using one of the human embryonic stem cell lines that I received from the NIH stem cell bank. Should I submit a "Request for Human Embryonic Stem Cell Line to be Approved for Use in NIH Funded Research"?
Unless your organization has the authority and/or rights pertaining to the human embryonic stem cell line (e.g., your organization is the owner, deriver or licensee or have written permission of the same to submit), you should not submit the request. You can see if a request has been submitted for the line you are using by checking http://grants.nih.gov/stem_cells/registry/pending.htm. (Draft requests can also be seen at http://grants.nih.gov/stem_cells/registry/draft_intent.htm.)
What types of stem cell research are governed by the NIH Guidelines for Human Stem Cell Research?
The NIH Guidelines for Human Stem Cell Research (Guidelines) effective on July 7, 2009, cover research with all human stem cells.
- Sections II and III apply specifically to human embryonic stem cells (hESCs).
- Section II details the eligibility criteria used by the NIH to determine if specific hESC lines are eligible for use in NIH-funded research.
- Section III explains the responsibility of the NIH funding recipients to assure that hESCs used in NIH-funded research are approved by NIH.
- Section IV details types of human pluripotent stem cell research that are not eligible for NIH funding, even when using hESCs that meet the Section II eligibility criteria. Section IV pertains to “hESCs and human induced pluripotent stem cells, i.e., human cells that are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers.” The prohibitions detailed in Section IV apply to all types of human pluripotent stem cells, including, but not limited to, those developed by methods such as the expression of genes involved in establishing pluripotency (e.g., the “Yamanaka factors”) and the culturing of embryonic germ cells from primordial germ cells.
- Section V details other types of research not eligible for NIH funding: the derivation of stem cells from human embryos and research using hESCs derived from sources other than human embryos created using in vitro fertilization for reproductive purposes.
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.
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.
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.
Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products and
References for the Regulatory Process for the Office of Cellular, Tissue and Gene Therapies
I am a scientist funded by the NIH. How many cell lines are available to me, and how do I get them?
The NIH has developed the NIH Human Embryonic Stem Cell Registry. This Registry lists all cell lines that are eligible for use in NIH-funded research.
The number of lines available for use in NIH-funded research continues to expand, as we continue to review new lines that have been submitted for the NIH's consideration. Please check the current NIH Human Embryonic Stem Cell Registry page for the most up-to-date list.
To obtain these cells, please fullow the "see details" link, which is found under the Cell Line name, within the NIH Human Embryonic Stem Cell Registry. This link includes more information about the selected cell line, as provided to the NIH. Some of this information may include: whether or not the cell line is available for distribution, the provider's name, telephone number, email address, and URL.
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 exactly do the current Guidelines say and what are you proposing to change?
The Final Guidelines, issued on 7/7/2009, state the following:
"For the purpose of these guidelines, “human embryonic stem cells” are cells that are derived from the inner cell mass of the blastocyst stage human embryos, are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers."
The proposed revision states:
"For the purpose of these Guidelines, ‘human embryonic stem cells (hESCs)’ are pluripotent cells that are derived from early stage human embryos, up to and including the blastocyst stage, are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers."
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.
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: http://www.uspto.gov/patents/process/search/.
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?
Yes, there is a statute and a policy that apply to the use of human fetal tissue in NIH funded research. The governing Federal statute on human fetal tissue research and transplantation is found in sections 498A and 498B of the PHS Act, 42 U.S.C. 298g-1 and 298g-2. The statute specifically prohibits any person from knowingly acquiring, receiving, or transferring any human fetal tissue for valuable consideration, and requires certain safeguards in transplantation research. Sections 4.1.14 and 126.96.36.199 of the NIH Grants Policy Statement, version 10/01/2013, detail NIH policy on research with human fetal tissue, per the statute.