Guidelines For Stem Cell Research Research Articles

O-003 Mechanics of human embryo compaction

Abstract Study question How the human embryo builds the blastocyst is crucial to improve ART, as morphology of human embryo is a prime determinant to assess implantation potential. Summary answer An evolutionarily conserved increase in cell contractility is required to generate the forces driving the compaction, which is the first morphogenetic event shaping the body. What is known already The shaping of the human embryo begins with compaction, during which cells come into close contact and form a tighter structure. ART studies suggest that human embryos fail compaction primarily because of defective adhesion. Based on our current understanding of animal morphogenesis, other morphogenetic engines, such as cell contractility, could be involved in shaping the human embryo. However, the molecular, cellular and physical mechanisms driving human embryo morphogenesis remain uncharacterized. Study design, size, duration A total of 54 frozen embryos have been used for this work. The use of human embryos donated for research was allowed by the Agence de la Biomédecine (approval number RE 17-011R) in compliance with the International Society for Stem Cell Research guidelines. Donated embryos were cryopreserved and stored at three different centers in Paris. Embryos were then transferred to the Institut Curie where they were immediately thawed and used for the research project. Participants/materials, setting, methods Using micropipette aspiration on human embryos, we mapped cell surface tensions during compaction. Drug inhibition and immunostaining of cell contractility and cell-cell adhesion in human embryos reveal what drives the surface tension responsible for compaction. To evaluate cell contractility we focused on F-actin and myosin motor proteins, for adhesion we focused on E-cadherin. Main results and the role of chance Mapping cell surface tensions during human compaction reveals a 4-fold increase of tension at the cell-medium interface, from 0.62 ± 0.04 to 2.35 ± 0.08 nN/µm (mean ± SEM of 147 measurements on 10 embryos, Student’s t test p < 10-5), while cell-cell contacts keep a steady tension ∼0.6 nN/µm. Therefore, increased tension at the cell-medium interface drives human embryo compaction, which is qualitatively similar to compaction in mouse embryos (from ∼0.2 to 0.4 nN/µm). Further comparison between human and mouse reveals qualitatively similar but quantitavely different mechanical strategies, with human embryos being mechanically least efficient. Inhibition of cell contractility and cell-cell adhesion in human embryos reveals that, while both cellular processes are required for compaction, adhesion involvement plays a permissive role. Only contractility controls the surface tension responsible for compaction. Interestingly, cell contractility and cell-cell adhesion exhibit distinct mechanical signatures when faulty. Analyzing the mechanical signature of naturally failing embryos, we find evidence that non-compacting embryos or partially compacting embryos with excluded cells have defective contractility. Limitations, reasons for caution Given the need to use embryos donated to research, which are valuable samples, our sample size is small but sufficient to show statistically significant differences. Moreover, these embryos come from infertile patients undergoing ART. Wider implications of the findings Excluded cells from compaction could be aneuploid to protect the embryonic tissue from chromosomal abnormalities. Is there a correlation between their mechanical signature and the fact that they may be aneuploid remains an open question. How physical laws are used to produce the breathtaking diversity of the shapes of life? Trial registration number ‘not applicable'

Modeling policy development: examining national governance of stem cell-based embryo models.

Researchers can now coax human pluripotent stem cells to imitate the structure and spontaneous self-organization of the developing human embryo. Although these stem cell-based embryo models present an advantageous alternative to embryo research, they also raise ethical and policy challenges. In 2021, the International Society for Stem Cell Research revised its Guidelines for Stem Cell Research and Clinical Translation, providing contemporaneous best practices for ethical conduct in the field. The Guidelines complement national governance frameworks; however, they also contain contentious and aspirational norms that might catalyze change in research practice and in the enactment of national policies. Using a sample of 11 research-intensive countries, the authors compare research policy frameworks against the International Society for Stem Cell Research Guidelines to showcase how developments in global and national policies might affect stem cell-based embryo model research governance and illustrate fertile areas for ethical reflection and policy development.

Mending the Gaps: Ethically Sensitive Cells and The Evolution of European Stem Cell Policy

The past decades witnessed the slow evolution of Europe's heterogeneous stem cell (SC) policy and substantial scientific advances in the field. Parallel to these developments, professional organizations have grown in influence. With the recently revised International Society for Stem Cell Research's Guidelines as a backdrop, we address the evolution of SC policies in 46 European countries and discuss how they fare against evolving ethical standards, societal views, and scientific advances. We identify areas of convergence, divergence, and the suitability of extant governance mechanisms to meet their stewardship roles. Europe represents a rich casestudy as it encompasses a wide range of policy approaches present worldwide. Comparative studies provide an opportunity to promote insight into national frameworks and to foster international harmonization.

Comparison of the 2021 International Society for Stem Cell Research (ISSCR) guidelines for "laboratory-based human stem cell research, embryo research, and related research activities" and the corresponding Japanese regulations.

This paper presents a comparison of the 2021 guidelines for stem cell research and clinical translation outlined by the International Society for Stem Cell Research (ISSCR) with the current regulations in Japan regarding the performance of such research. This paper provides a convenient English-language summary of the Japanese regulations, and illustrates the difference between the ISSCR guidelines and Japanese regulations regarding the conditions of implementation of study activities using human embryos or stem cells, for researchers outside Japan. The regulations governing the performance of research activities using human embryos or stem cells in Japan are relatively complex and comprise a range of laws and guidelines; the specific rules applied depend on the characteristics of each study. Therefore, even similar research activities may differ in terms of not only the guidelines or laws implemented, but also the procedures required. Such situations may confuse researchers.

論胚胎的道德地位——儒家倫理的視角

LANGUAGE NOTE | Document text in Chinese; abstract also in English.
 For 40 years, international rules have limited human embryo research to the first 14 days of embryonic development. On May 26, 2021, in its latest guidelines for stem cell research and its medical applications, the International Society for Stem Cell Research eased the 14-day restriction. This raises myriad ethical issues. At their core is the debate over the moral status of embryos, which exposes ethical conflicts between cultural perspectives. This article discusses the moral status of embryos and argues from the perspective of Confucian ethics that the 14-day limit should not be waived at the present moment.

Heritable human genome editing is ‘currently not permitted’, but it is no longer ‘prohibited’: so says the ISSCR

The Guidelines for Stem Cell Research and Clinical Translation, recently issued by the International Society for Stem Cell Research (ISSCR), include a number of substantive revisions. Significant changes include: (1)...

Human embryo research, stem cell-derived embryo models and invitro gametogenesis: Considerations leading to the revised ISSCR guidelines.

SummaryThe ISSCR Guidelines for Stem Cell Research and Clinical Translation were last revised in 2016. Since then, rapid progress has been made in research areas related to in vitro culture of human embryos, creation of stem cell-based embryo models, and in vitro gametogenesis. Therefore, a working group of international experts was convened to review the oversight process and provide an update to the guidelines. This report captures the discussion and summarizes the major recommendations made by this working group, with a specific emphasis on updating the categories of review and engagement with the specialized scientific and ethical oversight process.

ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 update

SummaryThe International Society for Stem Cell Research has updated its Guidelines for Stem Cell Research and Clinical Translation in order to address advances in stem cell science and other relevant fields, together with the associated ethical, social, and policy issues that have arisen since the last update in 2016. While growing to encompass the evolving science, clinical applications of stem cells, and the increasingly complex implications of stem cell research for society, the basic principles underlying the Guidelines remain unchanged, and they will continue to serve as the standard for the field and as a resource for scientists, regulators, funders, physicians, and members of the public, including patients. A summary of the key updates and issues is presented here.

ISSCR's Guidelines for Stem Cell Research and Clinical Translation: Supporting development of safe and efficacious stem cell-based interventions.

The ISSCR’s revised Guidelines for Stem Cell Research and Clinical Translation reflect the organization’s commitment to opposing premature commercialization of stem cell-based interventions and supporting the development of products that meet stringent ethical, scientific, and regulatory standards. The Guidelines contain five important new recommendations concerning clinical translation of stem cell products.

ISSCR guidelines for the transfer of human pluripotent stem cells and their direct derivatives into animal hosts.

SummaryThe newly revised 2021 ISSCR Guidelines for Stem Cell Research and Clinical Translation includes scientific and ethical guidance for the transfer of human pluripotent stem cells and their direct derivatives into animal models. In this white paper, the ISSCR subcommittee that drafted these guidelines for research involving the use of nonhuman embryos and postnatal animals explains and summarizes their recommendations.

Research guidelines for embryoids

Human embryo models formed from stem cells—known as embryoids—allow scientists to study the elusive first stages of human development without having to experiment on actual human embryos. But clear ethical...

General requirements for stem cells.

The standard ‘General requirements for stem cells’ is the first set of general guidelines for stem cell research and production in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the classification, ethical requirements, quality requirements, quality control requirements, detection control requirements and waste disposal requirements of stem cells, which is applicable to stem cell research and production. It was firstly released by the Chinese Society for Cell Biology on 1 August 2017 and was further revised on 30 April 2020. We hope that publication of these guidelines will promote institutional establishment, acceptance, and execution of proper protocols, and accelerate the international standardization of stem cells for clinical development and therapeutic applications.

Ethical Guiding Principles of "Do No Harm" and the "Intention to Save Lives" in relation to Human Embryonic Stem Cell Research: Finding Common Ground between Religious Views and Principles of Medical Ethics.

One of the goals of medicine is to improve well-being, in line with the principle of beneficence (do no harm). Likewise, scientists claim that the goal of human embryonic stem cell (hESC) research is to find treatments for diseases. In hESC research, stem cells are harvested from a 5-day-old embryo. Surplus embryos from infertility treatments or embryos created for the sole purpose of harvesting stem cells are used in the research, and in the process the embryos get destroyed. The use of human embryos for research purpose raises ethical concern. In this context, the religious leaders play the role to be the moral compass and "reality check" to engage with the public. In Malaysia, the Ministry of Health has outlined the Guidelines for Stem Cell Research and Therapy, reflecting on Islamic principles. Since there has not been much focus on the viewpoints of other faiths in Malaysia, this study attempts to (i) explore the ethical guiding principles deliberated by religious leaders from the Buddhist, Hindu and Catholic traditions and (ii) identify if there is a common ground between the mainstream religious views and principles of medical ethics, in relation to hESC research. Eleven religious leaders representing the Buddhist, Hindu and Catholic traditions were interviewed. Interestingly, though reasoning of religious leaders came from different angles, their underlying concerns revolve around the values of "do no harm" and "intention to save lives". These values are also the key principles in medical ethics. The findings are applied to answer the question as to whether religious and medical guiding principles can co-exist and complement in ethical decision-making, without compromising the values.

Regulation of Stem Cell Technology in Malaysia: Current Status and Recommendations.

Stem cell technology is an emerging science field; it is the unique regenerative ability of the pluripotent stem cell which scientists hope would be effective in treating various medical conditions. While it has gained significant advances in research, it is a sensitive subject involving human embryo destruction and human experimentation, which compel governments worldwide to ensure that the related procedures and experiments are conducted ethically. Based on face-to-face interviews with selected Malaysian ethicists, scientists and policymakers, the objectives and effectiveness of the current Guideline for Stem Cell Research and Therapy (2009) are examined. The study's findings show that the guideline is rather ineffective in ensuring good ethical governance of the technology. A greater extent of unethical conduct is likely present in the private medical clinics or laboratories offering stem cell therapies compared with the public medical institutions providing similar services, as the latter are closely monitored by the governmental agencies enforcing the relevant policies and laws. To address concerns over malpractices or unethical conduct, this paper recommends a comprehensive revision of the current stem cell guideline so that adequate provisions exist to regulate the explicit practices of the private and public stem cell sectors, including false advertising and accountability. The newly revised Malaysian stem cell guideline will align with the Guidelines for Stem Cell Research and Clinical Translation (2016) of the International Society for Stem Cell Research (ISSCR) containing secular but universal moral rules. However, a regulatory policy formulated to govern the technology remains the main thrust of empowering the guideline for compliance among the stakeholders.

The National Guidelines for Stem Cell Research (2017): What academicians need to know?

India recently updated its guidelines on stem cell research (SCR), the National Guidelines for Stem Cell Research 2017. It was drafted under a collaborative effort from the Indian Council of Medical Research and Department of Biotechnology. The new guidelines are a part of a continuous endeavor to tackle scientific, technical, as well as perceived challenges in the field of SCR. It seeks to facilitate safe, ethical, and regulated translational and clinical SCR by engaging all stakeholders proactively.

The stem cell market and policy options: a call for clarity

The stem cell market and policy options: a call for clarity

Perspectives on the New ISSCR Guidelines for Stem Cell Research and Clinical Translation

This review seeks to highlight key elements of the ISSCR 2016 Guidelines for Stem Cell Research and Clinical Translation, describe apparent influences on the Guidelines, provide an analysis of the utility and the potential impact of the Guidelines on the field of stem cell research, and propose considerations for the future versions of the Guidelines. Part ethical code of conduct, part “how-to” instructions, and part policy declaration, this version of the Guidelines forms ISSCR’s most up-to-date recommendations and guidance on the topic of stem cell clinical translation. In the revised set of Guidelines, ISSCR has asserted the imperative of maintaining the highest ethical standards for clinical translation of stem cell research. The Guidelines set a sound foundation for self-regulation, not only communicating the Society’s position on what is legitimate stem cell research/treatment and what is not, but also fulfilling ISSCR’s mission of providing professional (and public) education regarding the specific steps that should be taken to translate basic research findings to the clinic. Future versions would benefit from more extensive references, including hyperlinks to regulatory authority guidance documents; and improved clarity of the writing style, including avoidance of vague descriptions and the addition of flow charts and/or tables.

Stem Cell Research and Clinical Translation: A Roadmap about Good Clinical Practice and Patient Care.

The latest research achievements in the field of stem cells led in 2016 to the publication of “Guidelines for Stem Cell Research and Clinical Translation” by the International Society for Stem Cell Research (ISSCR). Updating the topics covered in previous publications, the new recommendations offer interesting ethical and scientific insights. Under the common principles of research integrity, protection of patient's welfare, respect for the research subjects, transparency and social justice, the centrality of good clinical practice, and informed consent in research and translational medicine is supported. The guidelines implement the abovementioned publications, requiring rigor in all areas of research, promoting the validity of the scientific activity results and emphasizing the need for an accurate and efficient public communication. This paper aims to analyze the aforementioned guidelines in order to provide a valid interpretive tool for experts. In particular, a research activity focused on the bioethical, scientific, and social implications of the new recommendations is carried out in order to provide food for thought. Finally, as an emerging issue of potential impact of current guidelines, an overview on implications of compensation for egg donation is offered.

Guidelines for stem cell science and clinical translation.

The International Society for Stem Cell Research has released its updated guidelines for stem cell research in order to provide "assurance that stem cell research is conducted with scientific and ethical integrity and that new therapies are evidence-based." The guidelines were updated by a Guidelines Update Task Force consisting of twenty-five scientists, ethicists and experts in health care policy from nine countries. The chairpersons of this task force are Jonathan Kimmelman, George Daley and Insoo Hyun. There is no representative from India; the only person of Indian origin on it, Mahendra Rao, represents The New York Stem Cell Foundation.

Setting Global Standards for Stem Cell Research and Clinical Translation: The2016 ISSCR Guidelines.

The International Society for Stem Cell Research (ISSCR) presents its 2016 Guidelines for Stem Cell Research and Clinical Translation (ISSCR, 2016). The 2016 guidelines reflect the revision and extension of two past sets of guidelines (ISSCR, 2006, ISSCR, 2008) to address new and emerging areas of stem cell discovery and application and evolving ethical, social, and policy challenges. These guidelines provide an integrated set of principles and best practices to drive progress in basic, translational, and clinical research. The guidelines demand rigor, oversight, and transparency in all aspects of practice, providing confidence to practitioners and public alike that stem cell science can proceed efficiently and remain responsive to public and patient interests. Here, we highlight key elements and recommendations in the guidelines and summarize the recommendations and deliberations behind them.