Induced Pluripotent Stem Cells and Their Use in Human Models of Disease and Development.

The discovery of somatic cell nuclear transfer proved that somatic cells can carry the same genetic code as the zygote, and that activating parts of this code are sufficient to reprogram the cell to an early developmental state. The discovery of induced pluripotent stem cells (iPSCs) nearly half a century later provided a molecular mechanism for the reprogramming. The initial creation of iPSCs was accomplished by the ectopic expression of four specific genes (OCT4, KLF4, SOX2, and c-Myc; OSKM). iPSCs have since been acquired from a wide range of cell types and a wide range of species, suggesting a universal molecular mechanism. Furthermore, cells have been reprogrammed to iPSCs using a myriad of methods, although OSKM remains the gold standard. The sources for iPSCs are abundant compared with those for other pluripotent stem cells; thus the use of iPSCs to model the development of tissues, organs, and other systems of the body is increasing. iPSCs also, through the reprogramming of patient samples, are being used to model diseases. Moreover, in the 10 years since the first report, human iPSCs are already the basis for new cell therapies and drug discovery that have reached clinical application. In this review, we examine the generation of iPSCs and their application to disease and development.

Throwing the baby out with the bathwater: a critique of Sparrow's inclusive definition of the term 'in vitro eugenics'.

Sparrow highlights three potential applications of in vitro eugenics, that is, (a) research into the heredity of genetic disorders, (b) production of cell lines with specific genotypes, and (c) breeding better babies, and points to the need for researchers to discuss in advance the potential ethical problems that may emerge if the realization of this technology occurs in the near future. In this commentary, we pose a question for the sake of discussion. Is it, in fact, appropriate to label all three applications raised by Sparrow as eugenics? By doing so, an unnecessary level of concern might be borne among the public, and as a result, the sound development of this specialized technology would be affected. If the label of eugenics is to be applied to all three of these applications, then Sparrow must justify how he perceives (a) and (b) as not inherently different from (c).

Attitudes of patients with IVF/ICSI toward human embryo in vitro culture beyond 14 days.

When the International Society for Stem Cell Research revised its 2021 guidelines, it reversed its ban on the in vitro culture of human embryos beyond 14 days. However, despite widespread recognition of the importance of public debate on embryo research, it remains unclear how patients who have undergone in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) perceive this change in the guidelines. Three focus group interviews were conducted with IVF/ICSI patients to understand their opinions on extending the in vitro culture of human embryos beyond 14 days. Thematic analysis revealed a primarily favorable attitude toward the extension of in vitro embryo culture, identifying six reasons for this positive perspective. However, two reasons for negative attitudes were identified, along with some concerns that need to be addressed. To facilitate an open discussion, the following suggestions were made to the government and scientific community. The government and scientific community should provide sufficient knowledge to IVF/ICSI patients about research before discussions. It's important to consider diverse views on embryo models, including distrust and resistance. Ensuring IVF/ICSI patients' psychological safety is essential. "Public conversations" with citizens, including IVF/ICSI patients, should be promoted, and their opinions should be considered as part of a broader public spectrum.

Opinions on research involving human embryo models by researchers and the general public.

Rules and ethical considerations regarding research on embryo models have been debated across numerous countries. In this paper, we provide insights from our attitude survey conducted among Japanese researchers, including members of the Japanese Society for Regenerative Medicine, and among the general public residing in Japan, the US, the UK, Canada, and Australia. Our survey revealed that many researchers expressed the need for clear guidelines for embryo model research. Furthermore, a minority but significant portion of the general public in each country expressed opposition to research on embryo models but did not oppose research involving real embryos.

Survey of Japanese researchers and the public regarding the culture of human embryos in vitro beyond 14 days.

The International Society for Stem Cell Research (ISSCR) has eliminated its prohibition on research involving the culturing of human embryos beyond 14 days within the updated 2021 guidelines. We conducted a survey of Japanese researchers working in stem cell- or embryo-related research (n = 535) and the public (n = 3,000) about their attitudes toward the 14-day rule. Among the researchers, 46.2% agreed that embryos could be cultured beyond 14 days, a result that was slightly lower among the public (37.9%). Among those that disagreed with embryo culturing beyond 14 days, 9.5% of researchers and 5.1% of the public agreed with culturing embryos within 14 days. Among the public, higher comprehension levels correlated with both agreement and disagreement with the culture of embryos beyond 14 days compared with "cannot judge." Further research and pubic discourse are necessary in order to better understand the factors informing participant decisions regarding the 14-day rule.

Attitudes towards human fetal tissue research: Survey of researchers and the public in Japan.

Introduction: The rules for human fetal tissue (HFT) research in Japan are unclear. Methods: In this paper, we conducted a web survey to examine the attitudes of Japanese researchers (n=535) and the public (n=3,000) toward HFT research. Results: The results demonstrated that 5.8% of researchers and 18.8% of the public explicitly opposed HFT research, and 71.8% of the researchers thought that the rules for HFT research need to be clarified. Even among researchers who intended to consider conducting HFT research, 74.2% responded that the rules should be clarified. Although different from attitudes to make decisions regarding HFT donation, being non-religious and in their reproductive age among women in the public group were factors for accepting attitudes toward HFT research. Conclusion: To establish the rules, it is necessary to develop a system that can adequately protect vulnerable women who are asked to provide HFT.

A comparative analysis of attitudes toward stem cell research and regenerative medicine between six countries - A pilot study.

Introduction: Breakthroughs in stem cell research (SCR) and regenerative medicine (RM) have attracted significant public attention worldwide. Simultaneously, scientific communities and science policies have tried to establish appropriate governance of SCR and RM. In this context, effective communication between scientific communities and the public is regarded as a key factor. However, the diversity of public attitudes and interests has not been sufficiently examined, especially the differences across countries. Methods: We conducted an international comparison of public attitudes toward SCR and RM. We circulated an internet questionnaire among people in six countries: Japan, South Korea, the United States, the UK, Germany, and France. We collected 100 valid responses from each country, and a total of 600 responses were obtained. Results: Our key findings are the diversity of interests in RM, which can be expressed as user pragmatism, governance and handling of RM, risk, and benefit, and scientific interests. The priority of interests varied across the six countries, and the variations may be influenced by the political, social, cultural, and media contexts of SCR and RM in each country. Conclusion: The implications can contribute to a deeper understanding of the diversity of public attitudes, and bring about an appropriate examination of a wide range of ethical and social concerns of SCR and RM in global contexts.

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.

[Stem cell research and science and technology policy in Japan].

In this paper I review the present condition of the regeneration medicine research using pluripotency and a somatic stem cell, and I describe the subject of the science and technology policy in Japan towards realization of regeneration medicine. The Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) supported research promotion by the prompt action in 2007 when establishment of the iPS cell was reported by Shinya Yamanaka. Although the hospitable support of the Japanese government to an iPS cell is continued still now, there are some problems in respect of the support to other stem cell researches, and industrialization of regeneration medicine. In order to win a place in highly competitive area of investigation, MEXT needs to change policy so that funds may be widely supplied also to stem cell researches other than iPS cell research.

A Comparative Analysis of Attitudes on Communication Toward Stem Cell Research and Regenerative Medicine Between the Public and the Scientific Community.

Owing to the rapid progress in stem cell research (SCR) and regenerative medicine (RM), society's expectation and interest in these fields are increasing. For effective communication on issues concerning SCR and RM, surveys for understanding the interests of stakeholders is essential. For this purpose, we conducted a large-scale survey with 2,160 public responses and 1,115 responses from the member of the Japanese Society for Regenerative Medicine. Results showed that the public is more interested in the post-realization aspects of RM, such as cost of care, countermeasures for risks and accidents, and clarification of responsibility and liability, than in the scientific aspects; the latter is of greater interest only to scientists. Our data indicate that an increased awareness about RM-associated social responsibility and regulatory framework is required among scientists, such as those regarding its benefits, potential accidents, abuse, and other social consequences. Awareness regarding the importance of communication and education for scientists are critical to bridge the gaps in the interests of the public and scientists. Stem Cells Translational Medicine 2018;7:251-257.

20 Years of Human Pluripotent Stem Cell Research: It All Started with Five Lines.

November 2018 marks the 20th anniversary of the seminal human embryonic stem cell (hESC) publication, which reported the initial hESC derivations and launched the field of human pluripotent stem cell research. To commemorate this significant milestone, we reflect on the scientific, economic, and clinically relevant impact of this groundbreaking achievement.

Science communication in regenerative medicine: Implications for the role of academic society and science policy.

It is essential to understand the hurdles, motivation, and other issues affecting scientists' active participation in science communication to bridge the gap between science and society. This study analyzed 1115 responses of Japanese scientists regarding their attitudes toward science communication through a questionnaire focusing on the field of stem cell and regenerative medicine. As a result, we found that scientists face systemic issues such as lack of funding, time, opportunities, and evaluation systems for science communication. At the same time, there is a disparity of attitudes toward media discourse between scientists and the public.

Recognition of, interest in, and understanding of induced pluripotent stem cells and regenerative medicine in Japanese students.

We studied the recognition of, interest in, and understanding of induced pluripotent stem (iPS) cells and regenerative medicine in a total of 2659 junior high school, senior high school, and university students. The number of valid responses received was 2396 (90.1%). We report the following seven observations [1]. More than 80% of students reported recognition of iPS cells, regenerative medicine, and Professor Shinya Yamanaka, and a similar number were interested in and supportive of regenerative medicine [2]. Regenerative medicine was viewed as a medical treatment option. However, females were more cautious regarding use of regenerative medicine as a treatment compared with males [3]. Approximately 90% of students were interested in the latest medical care. Among the new treatment methods, they more frequently selected those that they were more familiar with and perceived less invasive to be ideal [4]. Regarding organ or tissue donation in regenerative medicine, students focused more on the characteristics of the donors [5]. Approximately 90% were supportive of storing their own cells. However, approximately 50% of students supported storing iPS cells for use in regenerative medicine [6]. Most students were anxious regarding the side effects, safety, and treatment costs of regenerative medicine, but supported the need of education regarding regenerative medicine [7]. More than 70% of students thought that education of regenerative medicine was necessary for the public. These findings suggest the importance of social approach, in addition to medical approach such as research and development, to improve QOL in community by developing the public understanding of regenerative medicine through science communication and school education, for the establishment of systems to promote this field.

Transcriptional profiling of hematopoietic stem cells by high-throughput sequencing.

Microarray analysis has made it feasible to carry out extensive gene expression profiling in a single assay. Various hematopoietic stem cell (HSC) populations have been subjected to microarray analyses and their profiles of gene expression have been reported. However, this approach is not suitable to identify novel transcripts or for profiling of genes with low expression levels. To obtain a detailed gene expression profile of CD34(-)c-Kit(+)Sca-1(+)lineage marker-negative (Lin(-)) (CD34(-)KSL) HSCs, we constructed a CD34(-)KSL cDNA library, performed high-throughput sequencing, and compared the generated profile with that of another HSC fraction, side population (SP) Lin(-) (SP Lin(-)) cells. Sequencing of the 5'-termini of about 9,500 cDNAs from each HSC library identified 1,424 and 2,078 different genes from the CD34(-)KSL and SP Lin(-) libraries, respectively. To exclude ubiquitously expressed genes including housekeeping genes, digital subtraction was successfully performed against EST databases of other organs, leaving 25 HSC-specific genes including five novel genes. Among 4,450 transcripts from the CD34(-)KSL cDNA library that showed no homology to the presumable protein-coding genes, 29 were identified as strong candidates for mRNA-like non-coding RNAs by in silico analyses. Our cyclopedic approaches may contribute to understanding of novel molecular aspects of HSC function.