Stem Cell Research Oversight (SCRO) Committee Purview
The SCRO Committee will provide oversight for all research on campus or involving campus faculty or staff that involves either:
- the use of human embryonic stem cells (hESCs) or their derivatives; or
- the introduction of human pluripotent stem cells (hPSCs), or their derivatives into non human animals at any embryonic, fetal, or postnatal stage, if an expected effect is that human cells will be integrated into the central nervous system, testes, or ovaries of the animal; or
- all research that
- involves preimplantation stages of human development, human embryos, or embryo-derived cells or
- entails the production of human gametes in vitro when such gametes are tested by fertilization or used for the creation of embryos; or
- the storage or disposition of human embryos or gametes obtained for the purposes of stem cell research.
- the storage and distribution of hESCs through a repository (as outlined in section 5)
The SCRO committee must review all human stem cell research regardless of the source of funding.
Human Embryonic Stem Cell Registries
National Institutes of Health (NIH) hESC Registry
Human embryonic stem cell (hESC) lines listed on the NIH Human Embryonic Stem Cell (hESC) Registry are eligible for use on the UW–Madison campus with approval from the SCRO Committee. These lines do not need additional provenance review and are eligible for use with federal funding.
UW–Madison hESC Registry
In addition, the SCRO Committee established and maintains the UW–Madison hESC Registry1. This registry includes hESCs with provenance already approved by the SCRO Committee. Lines on this registry cannot be used with federal funding.
hESC lines not currently listed on this registry must go through review of the documentation of provenance. Once the review is completed and approval is granted, the hESC line will be listed on the UW–Madison hESC Registry and will be eligible for use by UW-Madison investigators.
Provenance Approval Process
To ensure adherence to the basic ethical and legal principles of informed consent and protection of confidentiality, hESCs may be used by UW–Madison investigators only after documentation of their provenance has been provided to and approved by the UW–Madison SCRO committee. Documentation of provenance only needs to be provided prior to the first use of the hESCs in research falling within the UW–Madison SCRO committee’s purview. Upon approval by the SCRO committee, the hESCs will be listed on the UW–Madison hESC Registry
Documentation of Provenance: The SCRO Committee reviews documentation of the provenance of hESC lines before such lines may be added to the UW–Madison hESC Registry and used by University investigators. In determining which hESC lines may be used by University researchers, the SCRO Committee will consider whether the proper consent and additional criteria have been met, but may approve hESC lines for inclusion on the UW-Madison’s hESC Registry where procurement processes differ slightly from that specified. For a list of the criteria, please see UW– Madison Guidance for Documentation of Provenance. Consent documentation requirements are as follows:
- Embryos Created for Reproductive Purposes: For hESC lines derived from embryos originally created for reproductive purposes, but which are now in excess of clinical need, the UW–Madison SCRO committee must receive documentation that the embryo procurement process was approved by an Institutional Review Board (IRB) or appropriate institutional ethics committee and must receive a copy of the IRB-approved consent form(s) used during the embryo procurement process. If sperm or oocyte donors were used in this process, documentation of their consent to donate these excess embryos for research is not required2.
- Embryos Created for Research Purposes: For hESC lines derived from embryos created for research purposes through conventional (Standard or ICSI insemination) In Vitro Fertilization (IVF), the UW–Madison SCRO committee must receive documentation that the sperm and oocyte procurement processes were approved by an IRB or appropriate institutional ethics committee and must receive a copy of the IRB69 approved consent form(s) used during the sperm and oocyte procurement processes.
- Embryos Created by Somatic Cell Nuclear Transfer (SCNT): For hESC Lines Derived from Embryos Created for Research Purposes through SCNT, the UW–Madison SCRO committee must receive documentation that the oocyte and somatic cell procurement processes were approved by an IRB or appropriate institutional ethics committee and (1) The UW hESC Registry should not be confused with the NIH Human Embryonic Stem Cell Registry. (2) This conforms to the 2009 NIH Guidelines provision II.A.2 must receive a copy of the IRB-approved consent form(s) used during the oocyte and somatic cell procurement processes.
Oversight for introduction of hPSCs into non-human animals (chimeras).
A chimera is an organism composed of cells with different species origins. This includes any (non-human) animal into which human cells have been introduced. Human pluripotent stem cells (hPSCs) include human pluripotent stem cells from embryonic and non-embryonic sources.
UW–Madison Chimera Review
The UW–Madison’s Policy for Human Embryo and Human Pluripotent Stem Cell Research requires the SCRO Committee to review research involving the creation of chimeras when the chimeras are created in either of two ways:
- By introducing human embryonic stem cells (hESCs), or cells derived from hESCs, into an animal; or
- By introducing hPSCs obtained from non-embryonic sources, or cells derived from such hPSCs, into an animal, when one expected effect of the introduction is that human cells will be integrated into the central nervous system, testes, or ovaries of the animal.
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.3
Standard teratoma formation assays used to test whether cells are pluripotent must be reviewed 100 by the IACUC.
hPSC Line Limitations
The Committee will not approve the introduction of any cell lines with consent limitations, or cells derived from them, into animals during their embryonic stages of development.
Consent documents prohibit the following research utilizing hESCs WA01, WA07, WA09, WA13, WA14 (the original 5 Wisconsin lines):
- Mixing WA01, WA07, WA09, WA13, WA14 or their modifications with an intact 109 embryo, either human or non-human.
- Implanting WA01, WA07, WA09, WA13, WA14, their modifications, or their products 111 in a uterus.
- Attempting to make whole embryos with WA01, WA07, WA09, WA13, WA14 or their modifications with any method.
- Using WA01, WA07, WA09, WA13, WA14 or their modifications for therapeutic or commercial purposes, including the performance of services (including diagnostic services), for consideration or the production or manufacture of products for sale or distribution.
Carnegie Stages of Development and hPSC Limitations
The SCRO Committee uses the definition of the embryonic stage to extend through Carnegie Stage 23. In mice, this extends through E16, in rats through E17.5, in chicks through E10, and in pigs through E32.5. (See for information about other species.)
For researchers requesting to introduce pluripotent stem cells during the embryonic stages of development, researchers must provide rationale for introducing cells at the embryonic stage. In evaluating the application, the Committee will consider the following:
- The possibility the human material could affect the cognitive abilities of the animal research subject in ways that would be morally relevant.
- The possibility the that human gametes could form within animal research subjects, the breeding of which could then product a human conceptus.
- The breeding of animals into which hPSCs have been introduced.
- The introduction of hPSCs, or cells derived from such hPSCs, into non-human primate pre-implantation embryos.
- The introduction of pluripotent stem cells from any species into human pre-implantation embryos.
Embryo Research Oversight
- Research requiring comprehensive review by a SCRO process includes the following activities:
- Use of in vitro fertilization (IVF) embryos for research
- Research that generates human gametes when such research entails performing studies of fertilization that produce human embryos.
- Research involving the genetic manipulation of human embryos or gametes used to make embryos in vitro.
- Derivation of new pluripotent cell lines from human embryos.
- The scientific rationale for the need to generate new hESC lines, by whatever means, must be clearly presented, and the basis for the numbers of preimplantation embryos and oocytes needed should be justified. Evidence of Institutional Review Board or appropriate institutional ethics committee approval of the procurement process and a copy of the consent form used during the embryo procurement process should accompany such requests.
- Human embryos in existence at the University of Wisconsin as of the date of the approval of this policy may be used for the derivation of new stem cell lines so long as the consent process for such use utilized a consent form approved by the University’s Health Sciences IRB. Any request for generation of new hESC lines from these embryos and the protocol for research using the derived lines are still subject to SCRO review.
- The procurement processes for gametes or embryos used in the derivation of hESC lines in existence prior to the date of the approval of 166 the original policy (May 15, 2007) are not required to fully comply with this policy. However, the provenance of pre-existing hESC lines must still be documented in accordance with Sections 2 and 3.
- Research aimed at generating human totipotent cells that have the potential to sustain embryonic or later development.
- Research involving the in vitro culture of embryos or experimental generation of embryo-like structures that might manifest human organismal potential, to ensure minimal periods of in vitro culture, as justified by compelling scientific rationale but not beyond 14 days or formation of the primitive streak, whichever occurs first.
- Research in which human totipotent cells or pluripotent stem cells derived by any means are mixed with human embryos
- Research that is prohibited:
- In vitro culture of any intact human preimplantation embryo or organized embryo-like cellular structure with human organismal potential, regardless of derivation method, beyond 14 days or formation of the primitive streak, whichever occurs first.
- Experiments whereby human embryos or organized cellular structures that might manifest human organismal potential are gestated in any non-human animal uterus.
- Research in which human embryos produced by reprogramming of nuclei from somatic cells by nuclear transfer or comparable techniques are gestated in a human or animal uterus. Given current scientific, medical safety and ethical concerns, attempts at human reproductive cloning are prohibited.
- Research in which human embryos that have undergone modification of their nuclear genome are gestated in a human or animal uterus. Genome-modified human embryos include human embryos with engineered alterations to their nuclear DNA and/or embryos generated from a human gamete that has had its nuclear DNA modified, when such modifications will be inherited through the germ line. Given current scientific, medical safety and ethical concerns, attempts at germline editing are prohibited.
- Research in which animal chimeras incorporating human cells with the potential to form human gametes are bred to each other.
Human embryonic stem cell Storage and Distribution
- Definitions: For purposes of this policy, a repository is a facility designed to collect, store, and broadly distribute cells, and data or information about those cells, on an ongoing basis. It might also store and distribute DNA or other biomaterials.
- When members of a laboratory store cells for their own use, or share cells derived or engineered in that laboratory with other researchers in compliance with funder policies (e.g., NIH Grants Policy Statement, section 8.2.3: Sharing Research Resources, Oct. 2017) the laboratory does not become a repository for purposes of this policy. However, if a laboratory under the UW SCRO’s jurisdiction derives or obtains cells and stores them with the intent to broadly distribute them on an ongoing basis, it becomes a repository.
- Any repository under the jurisdiction of the UW-Madison SCRO that obtains, stores, and distributes hESC lines must have and follow policies and procedures to ensure that the hESC lines were derived ethically and in accordance with relevant laws and policies. It must have evidence-based, standardized methods and protocols in place to conduct biosafety screening; to characterize, maintain, store, and distribute cells; and to assess cell quality. It must document its activities. In particular, the repository’s policies must include:
- A secure system for protecting the privacy and confidentiality of donors and their medical information when materials retain codes or are accompanied by other identifiable information.
- A policy governing whether and how to return clinically significant information back to donors.
- A policy and system for disposal of cellular material, and documentation of that policy.
- Any investigator under the jurisdiction of the UW-Madison SCRO who derives new hESC lines is encouraged to deposit the lines in a repository from which they could be distributed. The deposit should occur no later than the end date of the investigator’s SCRO protocol.
- The SCRO Committee has authority to review policies and protocols for any repository under its jurisdiction.
- The University or any repository under the jurisdiction of the UW-Madison SCRO may refuse to accept hESC lines if they do not comply with this Policy.
Obtaining SCRO Protocol Approval and Conducting SCRO Approved Research
- Research falling within the scope of SCRO committee review can only be initiated after an on-line application has been submitted and the PI has received notification of SCRO Committee approval. Applications are initiated online at ARROW. The SCRO committee shall divide research proposals into three categories to determine the requisite level of oversight:
- Research that is permissible after expedited review. Expedited review will be conducted by one SCRO staff person and one committee member:
- Teratoma experiments to test pluripotency of human pluripotent stem cells (hPSCs) and purely in vitro human embryonic stem cell (hESC) research with pre-existing coded or anonymous hESC lines in general is approvable provided that notice of the research, documentation of the provenance of the cell lines, and evidence of compliance with any required Institutional Review Board, Institutional Animal Care and Use Committee, Institutional Biosafety Committee, or other mandated reviews is provided to the SCRO committee.
- Research that is permissible only after additional review and approval by the SCRO committee:
- The introduction of hPSCs, or their derivatives into non-human animals at any embryonic, fetal, or postnatal stage, if an expected effect is that human cells will be integrated into the central nervous system, testes, or ovaries of the animal. Particular attention will be paid to the probable pattern and effects of differentiation and integration of the human cells into the non-human animal tissues.
- Research in which personally identifiable information about the donors of the preimplantation embryos, gametes, or somatic cells from which the hESCs were derived is readily ascertainable by the investigator requires IRB and SCRO committee review and approval.
- Research that involves preimplantation stages of human development, human embryos, or embryo-derived cells or entails the production of human gametes in vitro when such gametes are tested by fertilization or used for the creation of embryos.
- Research that is not allowed (see Section 4.2)
- All applicable laws, policies, and guidelines pertaining to biosafety and animal care will apply to hESC research, and all applications will require UW biosafety and animal care approvals where appropriate.
- If a University investigator collaborates with an investigator at another institution, domestic or foreign, the SCRO committee may determine that the procedures prescribed by the other institution afford protections consistent with these guidelines and may approve the substitution of some or all of the other institution’s procedures for its own.
- The SCRO committee will maintain a list of UW-Madison investigators conducting hESC research along with a brief abstract about the type of research being performed and the hESC line(s) used in the research.
- hESC research directly for clinical application will be in compliance with all applicable Food and Drug Administration (FDA) regulations. If FDA requires that a link to the donor source be maintained, investigators and the University will document that the confidentiality of the donor is protected, that the donor is notified that a link will be maintained, and that, where applicable, federal human subjects protections and Health Insurance Portability and Accountability Act or other privacy protections are followed.
Committee Structure and Composition
- The University establishes a Stem Cell Research Oversight (SCRO) committee.
- The committee will include at least one representative of the public and may include persons with expertise in developmental biology, embryo development, stem cell research, molecular biology, and ethical and legal issues in hPSC research
- The SCRO committee will not substitute for the appropriate Institutional Review Board (IRB) but will provide an additional level of review and scrutiny warranted by the complex issues raised by hPSC research.
Amendments to Policy
- This policy may be amended by action of the SCRO committee subject to the written approval of the amendment by the Vice Chancellor for Research and Graduate Education.
- Amendments Adopted by SCRO on May 26, 2021, September 25, 2019, April 24, 2019, September 25, 2013, January 18, 2017, and December 20, 2017. Policy originally adopted on May 9, 2007.
- Amendments Approved by Vice Chancellor for Research and Dean of the Graduate School on December 2, 2013 and February 3, 2017. First approved on May 15, 2007.
1The UW hESC Registry should not be confused with the NIH Human Embryonic Stem Cell Registry.
2This conforms to the 2009 NIH Guidelines provision II.A.2
3NAS Guidelines 2016 section 2.1