Technical specifications for ethics review of human stem cell research.

The rapid advancement of human stem cell research and its expansion into emerging areas has resulted in an escalation of ethical challenges associated with these studies. As a result, there has been a corresponding increase in both the volume and complexity of institutional ethics reviews, coupled with higher expectations for the quality of the review process. In response to these challenges, this standard provides a comprehensive outline of the fundamental principles, content, types, and procedures of ethics review, specifically focusing on non-clinical human stem cell research. Its purpose is to provide clear operational and procedural guidelines, as well as recommendations, for the ethics review of such studies. The document was originally published by the Chinese Society for Cell Biology on August 30, 2022. It is our hope that the publication of these guidelines will facilitate the integration of ethical considerations and evaluations in a structured manner throughout the entire process of stem cell research, ultimately fostering a healthy and orderly development of the field.

The variability of judicial decisions in the stem cell industry in China.

As China's stem cell industry continues to develop, increasing disputes concerning stem cell-based interventions have been brought before the courts. Nonetheless, there is variability in the courts' understanding and attitude toward the regulatory attributes of these interventions, which to some extent has multifaceted impacts on the stem cell field.

Acting on ethics and governance of aging research.

Rapid advances in aging research and clinical translation come with numerous ethical and societal issues that the current regulatory framework may not be sufficient to address. To fill this gap, we propose a responsible and comprehensive governance framework to cope with these issues while maximizing the benefits of aging research.

Responsible governance of human germline genome editing in China†.

Considerable improvements have been made to gene editing technology, which has been increasingly applied to research involving humans. Nevertheless, human heritable germline genome editing is associated with a series of potential ethical, legal, and social risks, which have generated major controversies and discussions worldwide, especially after the "gene-edited babies" incident. Influenced by this incident, China has realized the importance of ethical governance in the field of life science and technology, has accelerated legislative and policy efforts in this field, and has gradually moved toward the direction of "precautionary" ethical governance. Black letter analysis, big data public opinion analysis, and other research methods are used in this paper. This paper explores the scientific background, ethical debates, and latest developments regarding China's regulatory framework for human germline gene editing after the "gene-edited babies" controversy and provides several recommendations on the future governance system of human germline gene editing in China. This paper argues that in recent years, the ethics governance of germline genome editing in China has been accelerated and great changes have been made. However, the regulatory system for germline genome editing requires further improvement in three aspects: coordination of legislation and agencies, establishment of an ethics review system at high levels, and public participation and education.

Knowledge graphs of ethical concerns of cerebral organoids.

OBJECTIVES: The rapid development of cerebral organoid technology and the gradual maturity of cerebral organoids highlight the necessity of foresighted research on relevant ethical concerns. We employed knowledge graphs and conducted statistical analysis with CiteSpace for a comprehensive analysis of the status quo of the research on the ethical concerns of cerebral organoids from a bibliometric perspective. MATERIALS AND METHODS: We performed a statistical analysis of published papers on cerebral organoid ethics, keyword co-occurrence graph, literature co-citation and knowledge clustering graph to examine the status of the ethics research, internal relationship between technological development and ethical research, and ethical concerns of the academia. Finally, we used a keyword time zone graph and related statistics to analyze and predict the trends and popular topics of future cerebral organoids ethics research. RESULTS: We demonstrated that although the ethical concerns of cerebral organoids have long been discussed, it was not until 2017 that the ethical issues began to receive more attention, when cerebral organoids were gradually mimicking the human brain more closely and increasingly being combined with chimera research. The recent key ethical concerns are primarily divided into three categories: concerns that are common in life sciences, specific to cerebral organoids, and present in cross-fields. These increasing ethical concerns are inherently related to the continual development of technology. The analysis pointed out that future research should focus on the ethical concerns of consciousness that are unique to cerebral organoids, ethical concerns of cross-fields, and construction and improvement of legislative and regulatory systems. CONCLUSIONS: Although research on cerebral organoids can benefit the biomedicine field, the relevant ethical concerns are significant and have received increasing attention, which are inherently related to the continual development of technology. Future studies in ethics regarding cerebral organoid research should focus on the ethical concerns of consciousness, and cross-fields, as well as the improvement of regulatory systems.

Requirements for human-induced pluripotent stem cells.

'Requirements for Human-Induced Pluripotent Stem Cells' is the first set of guidelines on human-induced pluripotent stem cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the technical requirements, test methods, and instructions for use, labeling, packaging, storage, transportation, and waste handling for human-induced pluripotent stem cells, which apply to the production and quality control of human-induced pluripotent stem cells. It was released by the Chinese Society for Cell Biology on 9 January 2021 and came into effect on 9 April 2021. We hope that the publication of these guidelines will promote institutional establishment, acceptance, and execution of proper protocols and accelerate the international standardization of human-induced pluripotent stem cells for applications.

Human retinal pigment epithelial cells.

'Human retinal pigment epithelial cells' is the first set of guidelines on human retinal pigment epithelial cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies technical requirements, test methods, inspection rules, instructions for usage, labelling requirements, packaging requirements, storage requirements and transportation requirements and waste disposal requirements for human retinal pigment epithelial cells, which is applicable to quality control during the process of manufacturing and testing of human retinal pigment epithelial cells. It was originally released by the Chinese Society for Cell Biology on 9 January 2021. We hope that publication of these guidelines will promote institutional establishment, acceptance and execution of proper protocols and accelerate the international standardization of human retinal pigment epithelial cells for applications.

Requirments for primary human hepatocyte.

'Requirements for Primary Human Hepatocyte' is the first set of guidelines on Primary Human Hepatocyte in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements and transportation requirements for Primary Human Hepatocyte, which is applicable to the quality control for Primary Human Hepatocyte. It was originally released by the China Society for Cell Biology on 9 January 2021. We hope that publication of these guidelines will promote institutional establishment, acceptance and execution of proper protocols and accelerate the international standardization of Primary Human Hepatocyte for applications.

Requirements for human haematopoietic stem/progenitor cells.

'Requirements for human haematopoietic stem/progenitor cells' is the first set of guidelines on human haematopoietic stem/progenitor cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the technical requirements, inspection methods, inspection rules, instructions for usage, labelling requirements, packaging requirements, storage requirements and transportation requirements for human haematopoietic stem/progenitor cells, which is applicable to the quality control for human haematopoietic stem/progenitor cells. We hope that publication of these guidelines will promote institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of human haematopoietic stem/progenitor cells for applications.

Human mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have attracted great interest for cell therapy and tissue regeneration due to their self-renewal capacity, multipotency and potent immunomodulatory effects on immune cells. However, heterogeneity of MSCs has become a prominent obstacle to limit their translation into practice, as cells from different tissue sources or each individual have great differences in their transcriptomic signatures, differentiation potential and biological functions. Therefore, there is an urgent need for consensus standard for the quality control and technical specifications of MSCs. 'Human Mesenchymal Stem Cells' is the latest set of guidelines on hMSC in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for hMSC, which is applicable to the quality control for hMSC. It was originally released by the China Society for Cell Biology on 9 January 2021. We hope that publication of these guidelines will facilitate institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of hMSC for clinical development and therapeutic applications.

Requirements for human cardiomyocytes.

'Requirements for human cardiomyocytes', jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human cardiomyocytes in China. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packing requirements, storage requirements, transportation requirements and waste disposal requirements for human cardiomyocytes, which is designed to normalize and standardize human cardiomyocyte research and production. It was originally released by the China Society for Cell Biology on 9 January 2021. We hope that the publication of this guideline will promote institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of human cardiomyocytes for applications.

Developing standards to support the clinical translation of stem cells.

Stem cells, which could be developed as starting or raw materials for cell therapy, hold tremendous promise for regenerative medicine. However, despite multiple fundamental and clinical studies, clinical translation of stem cells remains in the early stages. In contrast to traditional chemical drugs, cellular products are complex, and efficacy can be altered by culture conditions, suboptimal cell culture techniques, and prolonged passage such that translation of stem cells from bench to bedside involves not only scientific exploration but also normative issues. Establishing an integrated system of standards to support stem cell applications has great significance in efficient clinical translation. In recent years, regulators and the scientific community have recognized gaps in standardization and have begun to develop standards to support stem cell research and clinical translation. Here, we discuss the development of these standards, which support the translation of stem cell products into clinical therapy, and explore ongoing work to define current stem cell guidelines and standards. We also introduce general aspects of stem cell therapy and current international consensus on human pluripotent stem cells, discuss standardization of clinical-grade stem cells, and propose a framework for establishing stem cell standards. Finally, we review ongoing development of international and Chinese standards supporting stem cell therapy.

Stem cell 'therapy' advertisements in China: Infodemic, regulations and recommendations.

During the COVID-19 pandemic, in addition to the pandemic itself, a phenomenon called an 'infodemic'-defined by the World Health Organization as the spread of misleading information on the pandemic-has also gained attention. In the field of stem cell research, researchers and regulators have been fighting against false and misleading information, particularly advertisements for unproven and unauthorized stem cell-based interventions for decades. However, how existing legal and regulatory measures, which vary by country, can be employed to combat such false information is unclear. In this article, we examine the situation in China, where the spread of unauthorized stem cell 'therapies' has drawn patients from not only within China but also from abroad. First, we assess how and to what extent online advertisements promote unproven and unauthorized stem cell-based interventions directly to patients and prospective health consumers in China. Next, we survey the landscape for existing regulatory and administrative measures that may be used to combat false and misleading advertisements in this area. Finally, based on our analysis, we provide three main recommendations that may improve the effectiveness and efficiency of the regulatory measures in curtailing illegitimate advertising of unproven and unauthorized stem cell-based interventions in China. In conclusion, we also call for international collaboration among researchers and regulators in studying and strengthening regulations in this critical area that has so far been neglected in scholarly and policy discussions.

Ethical and Policy Considerations for Human Embryo and Stem Cell Research in China.

China's stem cell research policies are based on a cultural understanding that grants special protection to human embryos but does not assign them equivalent moral or legal status as fully developed humans. We discuss ethical considerations for embryo research and policy changes as China moves toward adopting internationally recognized rules.

Synergistic inhibition of characteristics of liver cancer stem-like cells with a combination of sorafenib and 8-bromo-7-methoxychrysin in SMMC-7721 cell line.

Sorafenib, a multi-kinase inhibitor, has shown its promising antitumor effect in a series of clinical trials, and has been approved as the current standard treatment for advanced hepatocellular carcinoma (HCC). 8-Bromo­7-methoxychrysin (BrMC) is a novel chrysin synthetic analogue that has been reported to inhibit the growth of various tumor cells and possess properties for targeting liver cancer stem cells (LCSCs) . The present study investigated the synergistic targeting effects on the properties of liver cancer stem-like cells (LCSLCs) by a combination of sorafenib and BrMC in SMMC-7721 cell line. We also investigated whether this effect involves regulation of HIF-1α, Twist and NF-κB protein. We found that the sphere-forming cells (SFCs) from the SMMC­7721 cells possessed the properties of LCSLCs. Sorafenib diminished the self-renewal capacity and downregulated the expression of stem cell biomarkers (CD133, CD44 and ALDH1) in a dose-dependent manner, while BrMC cooperated with sorafenib to strengthen this inhibition. Moreover, the combination of sorafenib and BrMC led to a remarkable decrease in the cellular migration and invasion, the downregulation of N-cadherin protein and upregulation of E-cadherin protein, and increase of cell apoptosis in LCSLCs. BrMC has a remarkable antagonistic effect on the upregulation of protein expression and DNA binding activity of NF-κB (p65) induced by sorafenib. In addition, our results indicated that the synergistic inhibition of sorafenib and BrMC on the characteristics of LCSLCs involves the downregulated expression of HIF-1α and EMT regulator Twist1. Collectively, the combination therapy of sorafenib and BrMC could be a new and promising therapeutic approach in the treatment of HCC.

Tubeimoside-1 suppresses breast cancer metastasis through downregulation of CXCR4 chemokine receptor expression.

To examine the effect of TBMS1on breast cancer metastasis, and investigate the potential mechanism by which Tubeimoside- 1 (TBMS1) inhibits the CXCR4 expression in breast cancer cells. The expression of CXCR4 in breast cancer cell lines was determined by immunoblotting and real-time PCR. The effect of TBMS1 on NF-κB binding activity was evaluated by EMSA assay and ChIP analysis. Cell proliferation and invasion were analyzed by MTT assay and transwell invasion assay, respectively. The effect of TBMS1 on breast cancer metastasis was further evaluated in a metastasis model of nude mice. TBMS1 suppressed the expression of CXCR4 through inhibition of NF-κB binding activity. TBMS1 inhibited CXCL12-induced invasion in breast cancer cells, while ectopic expression of CXCR4 abolished the inhibitive activity of TBMS1. TBMS1 suppressed breast cancer metastasis in the metastatic model of nude mice. TBMS1 suppressed the CXCR4-mediated metastasis of breast cancer by inhibiting NF-κB binding activity. [BMB Reports 2016; 49(9): 502-507].