|Front Matter (R1-R10)|
|Final Report (1-8)|
|Appendix A: National Institutes of Health Guidelines for Research Using Human Stem Cells (9-16)|
|Appendix B: Invited Participants at the August 7, 2009, Meeting of the Human Embryonic Stem Cell Research Advisory Committee (17-18)|
|Appendix C: National Academies' Guidelines for Human Embryonic Stem Cell Research, Amended as of May 2010 (19-36)|
|Appendix D: Committee Member and Staff Biographies (37-48)|
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research Appendix C National Academies’ Guidelines for Human Embryonic Stem Cell Research Amended as of May 20107 1.0 Introduction 2.0 Establishment of an Institutional Embryonic Stem Cell Research Oversight Committee 3.0 Procurement of Gametes, Morulae, Blastocysts or Cells for Generation of hES Generation Cell Lines 4.0 Derivation of hES Cell Lines 5.0 Banking and Distribution of hES Cell Lines 6.0 Research Use of hES Cell Lines 7.0 International Collaboration 8.0 Conclusion 1.0 INTRODUCTION In this chapter we collect all the recommendations made throughout the report and translate them into a series of formal guidelines. These guidelines focus on the derivation, procurement, banking, and use of human embryonic stem (hES) cell lines and some uses of human pluripotent (hPS) cell lines. They provide an oversight process that will help to ensure that research with hES cells is conducted in a responsible and ethically sensitive manner and in compliance with all regulatory requirements pertaining to biomedical research in general. The National Academies are issuing issues these guidelines 7 New or modified wording is indicated by underlining. Deleted wording is indicated by strikethrough.
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research for the use of the scientific community, including researchers in university, industry, or other private-sector research organizations who are conducting such research with non-federal funding. Researchers conducting federally-funded hES cell research should, however, note that the requirements of the National Institutes of Health (NIH)—available at http://stemcells.nih.gov/policy/2009guidelines.htm—supersede these National Academies’ Guidelines for certain sections (as noted below). 1.1 What These Guidelines Cover 1.1(a) These guidelines cover all derivation of hES cell lines and all research that uses hES cells derived from blastocysts and/or morulae made for reproductive purposes and later obtained for research from in vitro fertilization (IVF) clinics, blastocysts and/or morulae made specifically for research using IVF, somatic cell nuclear transfer (NT) into oocytes or by parthenogensis or androgenesis. 1.1(b) Some of the concerns addressed in this report are common to other types of human stem cell research; as such, certain of these Guidelines should also apply to those other types of research. For example, research that uses human adult stem cells, research that uses fetal stem cells or embryonic germ cells derived from fetal tissue; such research is covered by federal statutory restrictions at 42 U.S.C. 289g-2(a) and federal regulations at 45 CFR 46.210, research using hPS cells derived from non-embryonic sources, such as spermatogonial stem cells and “induced pluripotent” stem cells derived from somatic cells by introduction of genes or otherwise (so-called iPS cells), as well as other pluripotent cells yet to be developed; guidelines for hPS cells are collected in Section 7 below. Recommendations as to which guidelines apply to other hPS cells are collected in a new Section 7 below. Institutions and investigators conducting research with adult and fetal stem cells should also consider which individual provisions of these guidelines are relevant to their research.
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research 1.1(c) Research supported by NIH funds using NIH-approved hES cell lines is governed by NIH guidelines. 1.1(d) The guidelines do not cover research that uses nonhuman stem cells. 1.2 Reproductive Uses of NT These guidelines also do not apply to reproductive uses of nuclear transfer, which are addressed in the 2002 report Scientific and Medical Aspects of Human Reproductive Cloning, in which the National Academies recommended that “Human reproductive cloning should not now be practiced. It is dangerous and likely to fail.” Although these guidelines do not specifically address human reproductive cloning, it continues to be the view of the National Academies that research aimed at the reproductive cloning of a human being should not be conducted at this time. 1.3 Categories of hES Cell Research These guidelines specify categories of research that: Are permissible after currently mandated reviews and proper notification of the relevant research institution. Are permissible after additional review by an Embryonic Stem Cell Research Oversight (ESCRO) committee, as described in Section 2.0 of the guidelines. Should not be conducted at this time. Because of the sensitive nature of some aspects of hES cell research, these guidelines in many instances set a higher standard than is required by laws or regulations with which institutions and individuals already must comply. 1.3(a) hES Cell Research Permissible after Currently Mandated Reviews Purely in vitro hES cell research that uses previously derived hES cell lines is permissible provided that the ESCRO committee or equivalent body designated by the investigator’s institution (see Section 2.0) receives documentation of the provenance of the cell lines including (i) documentation of the use of an acceptable informed consent process that was approved by an Institutional Review Board (IRB) or foreign equivalent for their derivation (consistent with Section 3.6) and (ii) documentation of compliance with any
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research additional required review by an Institutional Animal Care and Use Committee (IACUC), Institutional Biosafety Committee (IBC), or other institutionally mandated review, if necessary. To determine whether the proposed research meets the requirements of this section, the ESCRO committee may choose to conduct an “expedited review” of such research proposals. In this context, expedited review means that the ESCRO committee chair or others designated by the committee chair act on behalf of the committee to determine that the hES cells have been acceptably derived (see Section 1.5) and report to the entire committee. All hES cell lines listed on the NIH Registry of approved lines are acceptable for use in research, subject to any restrictions imposed by NIH. Certain other lines may be considered acceptable for research using non-federal funds (see 1.5 below). 1.3(b) hES Cell Research Permissible Only After Additional Review and Approval Generation of new lines of hES cells by whatever means. Research involving the introduction of hES cells into nonhuman animals other than humans or primates8 at any stage of embryonic, fetal, or postnatal development. Particular attention should be paid to at least three factors: the extent to which the implanted cells colonize and integrate into the animal tissue; the degree of differentiation of the implanted cells; and the possible effects of the implanted cells on the function of the animal tissue. Research involving the introduction of hES cell into nonhuman primates at any stage of fetal or postnatal development. Particular attention should be paid to at least three factors: the extent to which the implanted cells colonize and integrate into the animal tissue; the degree of differentiation of the implanted cells; and the possible effects of the implanted cells on the function of the animal tissue. Research in which the identity of the donors of blastocysts, morulae, gametes, or somatic cells from which the hES cells were derived is readily ascertainable or might become known to the investigator. 8 “Nonhuman animals” has been changed to “animals other than human or primates” as the Guidelines do not permit the introduction of hES cells into humans or nonhuman primates (Section 1.3(c)(ii)).
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research 1.3(c) hES Cell Research That Should Not Be Permitted At This Time The following types of research should not be conducted at this time: Research involving in vitro culture of any intact human embryo, regardless of derivation method, for longer than 14 days or until formation of the primitive streak begins, whichever occurs first. Research in which hES cells are introduced into nonhuman primate blastocysts or in which any embryonic stem cells are introduced into human blastocysts. In addition: No animal into which hES cells have been introduced such that they could contribute to the germ line should be allowed to breed. 1.4 Obligations of Investigators and Institutions All scientific investigators and their institutions, regardless of their field, bear the ultimate responsibility for ensuring that they conduct themselves in accordance with professional standards and with integrity. In particular, people whose research involves hES cells should work closely with oversight bodies, demonstrate respect for the autonomy and privacy of those who donate gametes, morulae, blastocysts, or somatic cells and be sensitive to public concerns about research that involves human embryos. 1.5 Use of NIH-approved hES cell lines 1.5(a) It is acceptable to use hES cell lines that were approved in August 2001 for use in U.S. federally funded research. 1.5(b) ESCRO committees should include on their registry a list of NIH-approved cell lines that have been used at their institution in accord with the requirement in section 2.0 of the Guidelines. 1.5(c) Presence on the list of NIH-approved cell lines constitutes adequate documentation of provenance, as per Section 6.1 of the Guidelines.
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research 1.5 Acceptability of research using hES cell lines imported from other institutions or jurisdictions 1.5(a) Before approving use of hES and hPS cell lines imported from other institutions or jurisdictions, ESCRO committees should consider whether such cell lines have been “acceptably derived.” 1.5(b) “Acceptably derived” means that the cell lines were derived from gametes or embryos for which the donation protocol was reviewed and approved by an IRB or, in the case of donations taking place outside the United States, a substantially equivalent oversight body; consent to donate was voluntary and informed; donation was made with reimbursement policies consistent with these Guidelines; and donation and derivation complied with the extant legal requirements of the relevant jurisdiction. 1.5(c) ESCRO committees should include on their registry a list of cell lines that have been imported from other institutions or jurisdictions and information on the specific guidelines, regulations, or statutes under which the derivation of the imported cell lines was conducted. This is in accord with the requirement in section 2.0 of the Guidelines that calls for ESCRO committees to maintain registries listing the cell lines in use at their institutions. 2.0 ESTABLISHMENT OF AN INSTITUTIONAL EMBRYONIC STEM CELL RESEARCH OVERSIGHT COMMITTEE To provide oversight of all issues related to derivation and use of hES cell lines and to facilitate education of investigators involved in hES cell research, each many institutions currently require that research should have activities involving hES cells should be overseen by an Embryonic Stem Cell Research Oversight (ESCRO) committee. Although not required under the NIH Guidelines on Human Stem Cell Research, institutions conducting federally funded stem cell research are nevertheless likely to decide to maintain their ESCRO committees and use them for consultation, training, and any other functions appropriate to assist the institution and its researchers in evaluating and managing hES cell research. Institutions that conduct both federally funded and non-federally funded hES cell research, particularly if
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research this research involves the derivation of new cell lines, should maintain and use their ESCRO committees as they did prior to July 7, 2009. An ESCRO committee could be internal to a single institution or established jointly with one or more other institutions. Alternatively, an institution may have its proposals reviewed by an ESCRO committee of another institution, or by an independent ESCRO committee. An ESCRO committee should include independent representatives of the lay public as well as persons with expertise in developmental biology, stem cell research, molecular biology, assisted reproduction, and ethical and legal issues in hES cell research. It must have suitable scientific, medical, and ethical expertise to conduct its own review and should have the resources needed to coordinate the management of the various other reviews required for a particular protocol. A pre-existing committee could serve the functions of the ESCRO committee provided that it has the expertise recommended here and representation to perform the various roles described in this report. For example, an institution might elect to constitute an ESCRO committee from among some members of an IRB. But the ESCRO committee should not be a subcommittee of the IRB, as its responsibilities extend beyond human subject protections. Furthermore, much hES cell research does not require IRB review. The ESCRO committee should would: (a) Provide oversight over all issues related to derivation and use of hES cell lines. (b) Provide oversight over issues related to the use of hES cell lines not otherwise covered by NIH guidelines. (bc) Review and approve the scientific merit of research protocols. (cd) Review compliance of all in-house hES cell research with all relevant regulations and these guidelines. (de) Maintain registries of hES cell research conducted at the institution and hES cell lines derived or imported by institutional investigators. An institution conducting stem cell research should make information from the registries (including, but not necessarily limited to, project abstracts and source of funding) available to the public and the media through the institution’s Web site. (ef) Facilitate education of investigators involved in hES cell research. An institution that maintains its own ESCRO committee should also conduct periodic audits of the committee to verify that it is carrying out its responsibilities appropriately. Auditable records include documentation of decisions regarding the acceptability of research proposals and verification that cell
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research lines in use at the institution were acceptably derived (see Section 1.5). Institutions should make the results of these audits available to the public. An institution that uses an external ESCRO committee should nevertheless ensure that the registry and educational functions of an internal ESCRO committee are carried out by the external ESCRO committee on its behalf or internally by other administrative units. Institutions that use external ESCRO committees are also responsible for ensuring that these committees are likewise carrying out their responsibilities appropriately. 2.1 For projects that involve more than one institution, review of the scientific merit, justification, and compliance status of the research may be carried out by a single ESCRO committee if all participating institutions agree to accept the results of the review. 3.0 PROCUREMENT OF GAMETES, MORULAE, BLASTOCYSTS OR CELLS FOR GENERATION OF hES CELL LINES GENERATION 3.1 An IRB, as described in federal regulations at 45 CFR 46.107, should review all new procurement of all gametes, morulae, blastocysts, or somatic cells for the purpose of generating new hES or hPS cell lines. This includes the procurement of blastocysts and/or morulae in excess of clinical need from infertility clinics, blastocysts made through IVF specifically for research purposes, and oocytes, sperm, and somatic cells donated for development of hES cell lines derived through NT or by parthenogenesis or androgenesis; and hPS cells derived by any means that require human subjects review. 3.2 Consent for donation should be obtained from each donor at the time of donation. Even people who have given prior indication of their intent to donate to research any blastocysts and/or morulae that remain after clinical care should nonetheless give informed consent at the time of donation. Donors should be informed that they retain the right to withdraw consent until the blastocysts and/or morulae are actually used in cell line derivation. 3.3 When donor gametes have been used in the IVF process, resulting blastocysts and/or morulae may not be used for research without consent of all gamete donors. Written agreement at the time of gamete donation that one potential use of the blastocysts and/or morulae is embryo research will constitute sufficient consent.
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research 3.4 Payment and Reimbursement 3.4 (a) No payments, cash or in-kind, may be provided for donating blastocysts and/or morulae in excess of clinical need for research purposes. People who elect to donate stored blastocysts and/or morulae for research should not be reimbursed for the costs of storage prior to the decision to donate. 3.4(b) Women who undergo hormonal induction to generate oocytes specifically for research purposes (such as for NT) should be reimbursed only for direct expenses incurred as a result of the procedure, as determined by an IRB. Direct expenses may include costs associated with travel, housing, child care, medical care, health insurance, and actual lost wages. No payments beyond reimbursements, cash or in-kind, should be provided for donating oocytes for research purposes. Similarly, no payments beyond reimbursements should be made for donations of sperm for research purposes or of somatic cells for use in NT. 3.5 To facilitate autonomous choice, decisions related to the creation of embryos for infertility treatment should be free of the influence of investigators who propose to derive or use hES cells in research. Whenever it is practicable, the attending physician responsible for the infertility treatment and the investigator deriving or proposing to use hES cells should not be the same person. 3.6 In the context of donation of gametes, morulae, blastocysts, or somatic cells for hES cell research or for hPS cell research that requires human subjects review, the informed consent process, should, at a minimum, provide the following information.9 A statement that the blastocysts, gametes, morulae, blastocysts, or somatic cells will be used to derive hES or hPS cells for research that may include research on human transplantation. A statement that the donation is made without any restriction or direction regarding who may be the recipient of transplants of the cells derived, except in the case of autologous donation. A statement as to whether the identities of the donors will be readily ascertainable to those who derive or work with the resulting hES or hPS cell lines. 9 To be eligible for use in federally-funded research, the NIH guidelines specify specific elements for informed consent that may differ from the elements listed below.
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research If the identities of the donors are retained (even if coded), a statement as to whether donors wish to be contacted in the future to receive information obtained through studies of the cell lines. An assurance that participants in research projects will follow applicable and appropriate best practices for donation, procurement, culture, and storage of cells and tissues to ensure, in particular, the traceability of stem cells. (Traceable information, however, must be secured to ensure confidentiality.) A statement that derived hES or hPS cells and/or cell lines might be kept for many years. A statement that the hES or hPS cells and/or cell lines might be used in research involving genetic manipulation of the cells or the mixing of human and nonhuman cells in animal models. Disclosure of the possibility that the results of study of the hES or hPS cells may have commercial potential and a statement that the donor will not receive financial or any other benefits from any future commercial development. A statement that the research is not intended to provide direct medical benefit to the donor(s) except in the case of autologous donation. A statement that embryos will be destroyed in the process of deriving hES cells. A statement that neither consenting nor refusing to donate embryos for research will affect the quality of any future care provided to potential donors. A statement of the risks involved to the donor. In addition, donors could be offered the option of agreeing to some forms of hES cell research but not others. For example, donors might agree to have their materials used for deriving new hES cell lines but might not want their materials used, for example, for NT. The consent process should fully explore whether donors have objections to any specific forms of research to ensure that their wishes are honored. Investigators and stem cell banks are, of course, free to choose which cell lines to accept, and are not obligated to accept cell lines for which maintaining information about specific research use prohibitions would be unduly burdensome. New derivations of stem cell lines from banked tissues obtained prior to the adoption of these guidelines are permissible provided that the original donations were made in accordance with the legal requirements in force at the place and time of donation. This includes gametes, morulae, blastocysts, adult stem cells, somatic cells, or other tissue. In the event that these banked
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research tissues retain identifiers linked to living individuals, human subjects protections may apply. 3.7 Clinical personnel who have a conscientious objection to hES cell research should not be required to participate in providing donor information or securing donor consent for research use of gametes, morulae, or blastocysts. That privilege should not extend to the care of a donor or recipient. 3.8 Researchers may not ask members of the infertility treatment team to generate more oocytes than necessary for the optimal chance of reproductive success. An infertility clinic or other third party responsible for obtaining consent or collecting materials should not be able to pay for or be paid for the material obtained (except for specifically defined cost-based reimbursements and payments for professional services). 4.0 DERIVATION OF hES CELL LINES 4.1 Requests to the ESCRO committee for permission to attempt derivation of new hES cell lines from donated embryos, morulae, or blastocysts must include evidence of IRB approval of the procurement process (see Section 3.0 above). 4.2 The scientific rationale for the need to generate new hES cell lines, by whatever means, must be clearly presented, and the basis for the numbers of embryos, morulae, and blastocysts needed should be justified. 4.3 Research teams should demonstrate appropriate expertise or training in derivation or culture of either human or nonhuman ES cells before permission to derive new lines is given. 4.4 When NT experiments involving either human or nonhuman oocytes are proposed as a route to generation of hES cells, the protocol must have a strong scientific rationale. Proposals that include studies to find alternatives to donated oocytes in this research should be encouraged. 4.5 Neither blastocysts or morulae made using NT of human nuclei (whether produced with human or nonhuman oocytes) nor parthenogenetic or androgenetic human embryos may be transferred to a human or nonhuman uterus or cultured as intact embryos in vitro for longer than 14 days or until formation of the primitive streak, whichever occurs first.
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research 4.6 Investigators must document how they will characterize, validate, store, and distribute any new hES cell lines and how they will maintain the confidentiality of any coded or identifiable information associated with the lines (see Section 5.0 below). Investigators are encouraged to apply the same procedures and standards for characterization, validation, storage, and distribution to hPS cell lines. 5.0 BANKING AND DISTRIBUTION OF hES CELL LINES There are several models for the banking of human biological materials, including hES cells. The most relevant is the U.K. Stem Cell Bank. The guidelines developed by this and other groups generally adhere to key ethical principles that focus on the need for consent of donors and a system for monitoring adherence to ethical, legal, and scientific requirements. As hES cell research advances, it will be increasingly important for institutions that are obtaining, storing, and using cell lines to have confidence in the value of stored cells—that is, that they were obtained ethically and with the informed consent of donors, that they are well characterized and screened for safety, and that the conditions under which they are maintained and stored meet the highest scientific standards. Institutions engaged in hES research should seek mechanisms for establishing central repositories for hES cell lines—through partnerships or augmentation of existing quality research cell line repositories and should adhere to high ethical, legal, and scientific standards. At a minimum, an institutional registry of stem cell lines should be maintained. Institutions are encouraged to consider the use of the same procedures for banking and distribution of hPS cell lines. 5.1 Institutions that are banking or plan to bank hES cell lines should establish uniform guidelines to ensure that donors of material give informed consent through a process approved by an IRB and that meticulous records are maintained about all aspects of cell culture. Uniform tracking systems and common guidelines for distribution of cells should be established. 5.2 Any facility engaged in obtaining and storing hES cell lines should consider the following standards: Creation of a committee for policy and oversight purposes and creation of clear and standardized protocols for banking and withdrawals. Documentation requirements for investigators and sites that deposit cell lines, including
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research A copy of the donor consent form. Proof of Institutional Review Board approval of the procurement process. Available medical information on the donors, including results of infectious-disease screening. Available clinical, observational, or diagnostic information about the donor(s). Critical information about culture conditions (such as media, cell passage, and safety information). Available cell line characterization (such as karyotype and genetic markers). A repository has the right of refusal if prior culture conditions or other items do not meet its standards. A secure system for protecting the privacy of donors when materials retain codes or identifiable information, including but not limited to A schema for maintaining confidentiality (such as a coding system). A system for a secure audit trail from primary cell lines to those submitted to the repository. A policy governing whether and how to deliver clinically significant information back to donors. The following standard practices: Assignment of a unique identifier to each sample. A process for characterizing cell lines. A process for expanding, maintaining, and storing cell lines. A system for quality assurance and control. A website that contains scientific descriptions and data related to the cell lines available. A procedure for reviewing applications for cell lines. A process for tracking disbursed cell lines and recording their status when shipped (such as number of passages). A system for auditing compliance. A schedule of charges. A statement of intellectual property policies. When appropriate, creation of a clear Material Transfer Agreement or user agreement. A liability statement. A system for disposal of material.
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research Clear criteria for distribution of cell lines, including but not limited to evidence of approval of the research by an embryonic stem cell research oversight committee or equivalent body at the recipient institution. 6.0 RESEARCH USE OF hES CELL LINES Once hES cell lines have been derived, investigators and institutions, through ESCRO committees and other relevant committees (such as an IACUC, an IBC, or a radiation safety committee) should monitor their use in research. 6.1 Institutions should require documentation of the provenance of all hES cell lines, whether the cells were imported into the institution or generated locally. The institution should obtain evidence of IRB-approval of the procurement process and of adherence to basic ethical and legal principles of procurement as described in Section 1.3(a) and 1.5. In the case of lines imported from another institution, documentation that these criteria were met at the time of derivation will suffice. Listing on the NIH Registry will be sufficient evidence of acceptability of hES cell lines. 6.2 In vitro experiments involving the use of already derived and coded hES cell lines will not need review beyond the review described in Sections 1.3(a) and 6.1. 6.3 Each institution should maintain a registry of its investigators who are conducting hES cell research and ensure that all registered users are kept up to date with changes in guidelines and regulations regarding the use of hES cells. 6.4 All protocols involving the combination of hES cells with nonhuman embryos, fetuses, or adult vertebrate animals must be submitted to the local IACUC for review of animal welfare issues and to the ESCRO committee for consideration of the consequences of the human contributions to the resulting chimeras. (See also Section 1.3(c)(iii) concerning breeding of chimeras.) 6.5 Transplantation of differentiated derivatives of hES cells or even hES cells themselves into adult animals will not require extensive ESCRO committee review. If there is a possibility that the human cells could contribute in a major organized way to the brain of the recipient animal, however,
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research the scientific justification for the experiments must be strong, and proof of principle using nonhuman (preferably primate) cells, is desirable. 6.6 Experiments in which hES cells, their derivatives, or other pluripotent cells are introduced into nonhuman fetuses and allowed to develop into adult chimeras need more careful consideration because the extent of human contribution to the resulting animal may be higher. Consideration of any major functional contributions to the brain should be a main focus of review. (See also Section 1.3(c)(iii) concerning breeding of chimeras.) 6.7 Introduction of hES cells into nonhuman mammalian blastocysts should be considered only under circumstances in which no other experiment can provide the information needed. (See also Sections 1.3(c)(ii) and 1.3(c)(iii) concerning restrictions on breeding of chimeras and production of chimeras with nonhuman primate blastocysts.) 6.8 Research use of existing hES cells does not require IRB review unless the research involves introduction of the hES cells or their derivatives into patients or the possibility that the identity of the donors of the blastocysts, gametes, morulae, blastocysts, or somatic cells is readily ascertainable or might become known to the investigator. 7.0 RECOMMENDATIONS FOR RESEARCH USE OF NON-EMBRYO-DERIVED HUMAN PLURIPOTENT STEM CELLS (hPS CELLS) 7.1 Derivation Because non-embryo-derived hPS cells are derived from human material, their derivation is may be covered by existing IRB regulations concerning review and informed consent, depending on the source of the tissue used. No ESCRO committee review is necessary, although the IRB may always seek the advice of an ESCRO committee if this seems desirable. Where appropriate, tThe IRB review should consider proper consent for use of the derived hPS cells. Some of the recommendations for informed consent that apply to hES cells also apply to hPS cells (see Section 3.6), including informed consent to genetic manipulation of resulting pluripotent stem cells and their use for transplantation into animals and humans and potentially in future commercial development.
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research 7.2 Use in in Vitro Experiments Use of hPS cells in purely in vitro experiments need not be subject to any review beyond that necessary for any human cell line except that any experiments designed or expected to yield gametes (oocytes or sperm) should be subject to ESCRO committee review. 7.3 Use in Experiments Involving Transplantation of hPS Cells into Animals at any Stage of Development or Maturity 7.3(a) Research involving transplantation of pluripotent human cells derived from nonembryonic sources into nonhuman animals other than humans or primates at any stage of embryonic, fetal, or postnatal development should be reviewed by ESCRO committees and IACUCs, as are similar experiments that use hES cells. 7.3(b) ESCRO committees should review the provenance of the hPS cells as they review the provenance of hES cells (see section 1.5) to ensure that the cell lines were derived according to ethical procedures of informed consent as monitored by an IRB or equivalent oversight body. 7.3() Proposals for use of hPS cells in animals should be considered in one of the following categories: Permissible after currently mandated reviews and proper documentation [see Section 1.3(a)]: experiments that are exempt from full ESCRO committee review but not IACUC review (experiments that involve only transplantation into postnatal animals with no likelihood of contributing to the central nervous system or germ line). Permissible after additional review by an ESCRO committee, as described in Section 2.0 of the guidelines [see Section 1.3(b)]: experiments in which there is a significant possibility that the implanted hPS cells could give rise to neural or gametic cells and tissues. Such experiments need full ESCRO committee and IACUC review and would include generation of all preimplantation chimeras as well as neural transplantation into embryos or perinatal animals. Particular attention should be paid to at least three factors: the extent to which the implanted cells colonize and integrate into the animal tissue; the degree of differentiation
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research of the implanted cells; and the possible effects of the implanted cells on the function of the animal tissue. Should not be conducted at this time [see Section 1.3(c)] Experiments that involve transplantation of hPS cells into human blastocysts. Research in which hPS cells are introduced into nonhuman primate embryos, pending further research that will clarify the potential of such introduced cells to contribute to neural tissue or to the germ line. 7.4 Multipotent Neural Stem Cells It is also relevant to note that neural stem cells, although not pluripotent, are multipotent and may have the potential to contribute to neural tissue in chimeric animals. ESCRO committees should decide whether they wish to review and monitor such experiments with neural stem cells in a similar fashion. 7.5 Prohibition on Breeding No animal into which hPS cells have been introduced such that they could contribute to the germ line should be allowed to breed. 7.6 Guidance for Banking and Distribution Institutions should consider the value of banking and distributing hPS cells using the guidance and rules that are already in place for hES cells and the value of including hPS cell lines in their registries. 8.0 INTERNATIONAL COLLABORATION If a U.S.-based investigator collaborates with an investigator in another country, the ESCRO committee may determine that the procedures prescribed by the foreign institution afford protections consistent with these guidelines, and the ESCRO committee may approve the substitution of some of or all of the foreign procedures for its own. 9.0 CONCLUSION The substantial public support for hES cell research and the growing trend by many nonfederal funding agencies and state legislatures to support this field
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Final Report of the National Academies’ Human Embryonic Stem Cell Research Advisory Committee and 2010 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research requires a set of guidelines to provide a framework for hES cell research. In the absence of the oversight that would come with unrestricted of hES cell research that falls outside federal funding of this research, these guidelines will continue to offer reassurance to the public and to Congress that the scientific community is attentive to ethical concerns and is capable of self-regulation while moving forward with this important research. To help ensure that these guidelines are taken seriously, stakeholders in hES cell research—sponsors, funding sources, research institutions, relevant oversight committees, professional societies, and scientific journals, as well as investigators—should develop policies and practices that are consistent with the principles inherent in these guidelines. Funding agencies, professional societies, journals, and institutional review panels can provide valuable community pressure and impose appropriate sanctions to ensure compliance. For example, ESCROs and IRBs should require evidence of compliance when protocols are reviewed for renewal, funding agencies should assess compliance when reviewing applications for support, and journals should require that evidence of compliance accompanies publication of results. As individual states and private entities move increasingly into hES cell research, it will be important to initiate a national effort to provide a formal context in which the complex moral and oversight questions associated with this work can be addressed on a continuing basis. Both the state of hES cell research and clinical practice and public policy surrounding these topics are in a state of flux and are likely to be so for several years. Therefore, the committee believes that a national body mechanisms should be established to assess periodically the adequacy of the policies and guidelines proposed in this document and elsewhere and to provide a forum for a continuing discussion of issues involved in hES cell research. New policies and standards may be appropriate for issues that cannot now be foreseen. The organization that sponsors this body should be politically independent and without conflicts of interest, should be respected in the lay and scientific communities, and able to call on suitable expertise to support this effort.