This page assembles the sections of the Guidelines that specifically address research involving stem cell-based embryo models. Other sections of the Guidelines may be relevant to such research (e.g., Section 2.1 Review Process, Section 2.3 Procurement and Informed Consent of Human Biological Materials, and Section 4. Communications).
2.2.1 Category 1
2.2.1A: Category 1A. Research determined to be exempt from a specialized scientific and ethics oversight process after being assessed by the appropriate existing mandates and committees for laboratory research. Category 1A research includes the following activities:
- Research on stem cell culture systems that model specific stages of development or specific anatomic structures rather than the continuous development of an intact embryo or fetus. These would include but are not restricted to models of amnion formation, neural tube development, development of primordial germ cells, placental structures, 2D or 3D models of gastrulation or post-gastrulation events, and in vitro stem cell-derived organoids in culture that recapitulate most aspects of organ function, but not those that fall under subsequent categories.
2.2.1B: Category 1B. Research that is reportable to the entity or body responsible for the specialized scientific and ethics oversight process, but not normally subject to further or ongoing review, at the discretion of the entity responsible for the oversight process and subject to regulations and policies in the jurisdiction. Category 1B research includes the following activities:
- Research that entails the in vitro formation of human stem cell-based embryo models that are not intended to represent the integrated development of the entire embryo including its extraembryonic membranes.
Scientists pursuing Category 1A and B research are recommended to consult with appropriate institutional review committees or the committee or body responsible for the specialized scientific and ethics review process (see Recommendation 2.1.3) to determine the categorization of new research proposals. Committees with the jurisdiction over the relevant research should oversee the provenance of cells, tissues and derived human pluripotent stem cell lines to ensure that procurement and derivation is deemed acceptable according to the principles outlined in this document (see section 2.3.5) and is in compliance with rigorous scientific, legal, and ethical standards.
2.2.2 Category 2
2.2.2 Category 2. Forms of research with embryos, certain chimeras, and stem cell-based embryo models that are permissible only after review and approval through a specialized scientific and ethics review process. A comprehensive review should be coordinated with other relevant oversight, such as that provided by human subjects review committees, in vitro fertilization (IVF) clinic oversight bodies, and animal research review processes (see 2.2.1), and the research should comply with local law and policy. All such research should have a compelling scientific rationale and necessitate the use of these materials rather than employ alternative models. The research should use the minimum number of embryos necessary to achieve the scientific objective. Forms of research requiring comprehensive review by a specialized review process encompass the following activities:
- Generation of stem cell-based embryo models that represent the integrated development of the entire embryo including its extraembryonic membranes. These integrated stem cell-based embryo models should be maintained in culture for the minimum time necessary to achieve the scientific objective.
2.2.3 Category 3
2.2.3B Category 3B: Prohibited research activities. Research under this category should not be pursued because of broad international consensus that such experiments lack a compelling scientific rationale or are widely considered to be unethical. Such research includes:
- Transfer of human stem cell-based embryo models to the uterus of either a human or animal host.
Public Representation of Science
Recommendation 4.1: The stem cell research community should promote accurate, current, balanced, and responsive public representations of stem cell research.
The high level of public and media interest in the field provides stem cell scientists with ample opportunities to communicate their findings through a variety of popular and social media channels. The research community is encouraged to responsibly engage interactively with the public through outreach and communications and by providing opportunities for public comment and feedback on scientific advances.
While such opportunities may allow scientists to gain recognition and understanding for their work among non-specialists, they also have the potential to fuel inaccurate public perceptions about the current state of scientific progress, potential for application, and associated risks and uncertainties (Kamenova and Caulfield, 2015). Scientists, clinicians, bioethicists, science communications professionals at academic and research institutions, and industry spokespersons should strive to ensure that benefits, risks, and uncertainties of stem cell science are not understated, misrepresented or overstated (see Recommendation 220.127.116.11). Additionally, due to public interest and concern in the ethics of human pluripotent stem cell research, and in order to ensure complete transparency of research and translational activities, the origin of stem cell materials should be clearly specified in all communications.
Care should be exercised throughout the science communication process, including in the promotion of research and translation activities, as well as in the presentation of scientific results, the use of social media, and in any communication with print and broadcast media. Particular caution should be exercised when preparing press releases and other types of promotional material. Researchers should make efforts to seek timely corrections of inaccurate or misleading public representations of research projects, achievements, or goals. Scientists should also be particularly careful about disclosing research findings that have not passed peer review, as premature reporting can undermine public confidence if findings are subsequently disproven. For example, if researchers post online preprints that have not been peer-reviewed, readers should be informed of the preliminary nature of such manuscripts.
Researchers must unintentionally avoid and correct inaccurate misconceptions in any communications regarding chimeras, genome editing, and other issues with a long history in the public imagination. While organoids, chimeras, embryo models, and other stem cell-based models are useful research tools offering possibilities for further scientific progress, limitations on the current state of scientific knowledge and regulatory constraints must be clearly explained in any communications with the public or media. Suggestions that any of the current in vitro models can recapitulate an intact embryo, human sentience or integrated brain function are unfounded overstatements that should be avoided and contradicted with more precise characterizations of current understanding. This is particularly relevant to brain organoids and human-animal chimeras, where any statements implying human cognitive abilities, human consciousness or self-awareness, as well as phrases or graphical representations suggesting human-like cognitive abilities risks misleading the public and sowing doubts about the legitimate nature of such research. Likewise, forward-looking statements on inherently uncertain developments, such as predictions on time required until clinical application, the likelihood of product approval, or speculation on the potential economic impact of currently unrealized technologies, must be accurate, circumspect, and restrained.
The stem cell community should work closely with communications professionals at their institution to create information resources that are easy to understand without oversimplifying, and that do not underplay risks and uncertainties or exaggerate potential benefits. Similarly, research-sponsoring institutions and communications professionals have a responsibility to ensure that any informational materials referring to research achievements adhere to these principles. Additionally, the scientists in charge of the research findings that are featured in informational materials should review and agree to the content prior to release. For potentially sensitive or high-profile cases, it is advisable to seek additional comments from independent experts to ensure objectivity and balance, place research in context of existing body of evidence, and help identify study limitations and alternative interpretations of key findings.
Stem cell-based embryo models: Advances in cellular engineering make possible the assembly, differentiation, aggregation, or re-association of cell populations in a manner that models or recapitulates key stages of embryonic development. Such experimental systems can provide essential insights into embryo and tissue development but raise concerns when such structures achieve complexity to the point where they might realistically manifest the ability to undergo further integrated development if cultured for additional time in vitro. There are two types of stem cell-based embryo models.
Non-integrated stem cell-based embryo models: These stem cell-based embryo models will experimentally recapitulate some, but not all aspects of the peri-implantation embryo, for example differentiation of the embryonic sac or embryonic disc in the absence of extraembryonic cells. These stem cell-based embryo models do not have any reasonable expectations of specifying additional cell types that would result in formation of an integrated embryo model. Gastruloids are an example of a non-integrated stem cell-based embryo model.
Integrated stem cell-based embryo models: These stem cell-based embryo models contain the relevant embryonic and extra-embryonic structures and could potentially achieve the complexity where they might realistically manifest the ability to undergo further integrated development if cultured for additional time in vitro. Integrated stem cell-based embryo models could be generated from a single source of cells, for example expanded potential human pluripotent stem cells capable of coordinately differentiating into embryonic and extraembryonic structures. Alternatively, integrated stem cell-based embryo models could also be generated through the formation of cellular aggregates where extraembryonic/embryonic cells from one source are combined with embryonic/extraembryonic cells from different sources to achieve integrated human development. This might include using non-human primate cells as one of the sources. Previous restrictions on preimplantation human embryo culture (the “14-day/primitive streak rule”) were not written to apply to integrated stem cell-based embryo models. Thus, these guidelines specify the imperative for specialized review when such research is designed to model the integrated development of the entire embryo including its extraembryonic membranes. A guiding principle of review should be that the integrated stem cell-based embryo models should be used to address a scientific question deemed highly meritorious by a rigorous review process. Blastoids are an example of an integrated stem cell model.