人胚胎干细胞建系研究中的伦理管理

目的：建立国人胚胎干细胞系递交国际干细胞库,并在此基础上建立既符合中国国情又得到国际认可的相关伦理管理体系。方法：在比尔盖茨基金会的资助下,与北京大学生命科学院再生生物学实验室合作,募集胚胎建立人胚胎干细胞系,在此过程中探讨可行的符合国际伦理原则的相关伦理管理机制。结果：成功建立了国人胚胎干细胞系及相关伦理管理体系。结论：进行干细胞研究时应充分重视伦理问题,国际干细胞伦理管理与中国相关伦理原则是可以有机结合的。     

人胚胎干细胞建系研究中的伦理管理

目的：建立国人胚胎干细胞系递交国际干细胞库,并在此基础上建立既符合中国国情又得到国际认可的相关伦理管理体系。方法：在比尔盖茨基金会的资助下,与北京大学生命科学院再生生物学实验室合作,募集胚胎建立人胚胎干细胞系,在此过程中探讨可行的符合国际伦理原则的相关伦理管理机制。结果：成功建立了国人胚胎干细胞系及相关伦理管理体系。结论：进行干细胞研究时应充分重视伦理问题,国际干细胞伦理管理与中国相关伦理原则是可以有机结合的。     

胚胎干细胞及诱导多能干细胞在胚胎毒性研究中的应用

药物对于生殖细胞或者早期胚胎的影响将会引起不孕或者种植前胚胎的发育异常,进而引起胚胎毒性或者是后代的畸形,因此药物的临床应用需要有可靠的实验数据证明其对胚胎的影响,而胚胎干细胞(embryonic stem cell,ESC)由于其无限增殖及多向分化的潜能而作为研究药物胚胎毒性的细胞模型得到广泛应用,以ESC为基础的胚胎干细胞实验(embryonic stem cell test,EST)是获得国际认可的胚胎毒性评价的体外替代方法,但是该实验方法的快速性和准确性存在一定的局限性,目前该细胞模型的研究主要集中于快速性和准确性的优化。新兴的诱导多能干细胞(induced pluripotent stem cells,i PSC),由于具有与ESC相似的增殖和分化特性,目前也被逐步应用于药物胚胎毒性的研究。     

人类植入前胚胎发育研究进展

随着近年无创成像技术、分子及基因组技术的发展,人类植入前胚胎发育的研究取得了相应进展。非侵入性实时成像法观察人类胚胎发育过程中最初3次有丝分裂可以预测囊胚发育的成败。目前世界各地多家体外受精（IVF）临床中心开始使用胚胎镜观察胚胎的卵裂时间和胚胎发育的空间模式。人类植入前胚胎发育的特征是重编程,包括精卵原核融合、表观遗传重编程和修饰、母源转录的全面退化和早期人类胚胎基因组激活,普遍认为在人胚胎发育的第3天即4-至8-细胞期胚胎基因组激活达高峰。谱系分化研究人类胚胎发育早期在8-细胞期每个细胞是独立的,但没有证据表明这一期不同细胞已经发生定向分化为滋养外胚层（TE）或内细胞团（ICM）。关于人单个卵母细胞的高精度全基因组测序、人类卵母细胞以及早期胚胎不同发育阶段基因转录组的动态变化已有报道。     

Ethical boundary-work in the embryonic stem cell laboratory

Most accounts of the ethics of stem cell research are de- contextualised reviews of the ethical and legal literature. In this chapter we present a socially embedded account of some of the ethical implications of stem cell research, from the perspectives of scientists directly involved in this area. Based on an ethnography of two leading embryonic stem cell laboratories in the UK, our data form part of the findings from a larger project mapping the scientific, medical, social and ethical dimensions of innovative stem cell treatment, focusing on the areas of liver cell and pancreatic islet cell transplantation. We explore three key issues: what individual scientists themselves view as ethical sources of human embryos and stem cells; their perceptions of human embryos and stem cells; and how scientists perceive regulatory frameworks in stem cell research. We argue that these dimensions of laboratory practice are all examples of 'ethical boundary-work', which is becoming an integral part of the routine practice and performance of biomedical science. Our work adds to the relatively few sociological studies that explore ethics in clinical settings and to an even smaller body of work that explores scientists' views on the ethical issues relating to their research.     

Würde am Lebensbeginn

Ethical questions in relation to human embryos in vitro are today raised by reproductive medicine, preimplantation genetic diagnosis and stem cell research. Various discourses - biological, political and medical - describe the embryo from different perspectives. Empirical investigations of the perceptions and concerns of patients in IVF treatments provide important insights. Referring to a variety of discourses and perspectives, the paper develops an ethical analysis of the responsibility for embryos in vitro, with a special emphasis on the relationships involved. In the context of current discussions about the moral status of the embryo, the paper differentiates between four different meanings of "potentiality" of the embryo: (a) external potentiality, (b) the tendency towards a developmental pathway, (c) the transitive determination by a program, (d) preformation. For different reasons, (a), (c) and (d) are rejected. On the basis of potentiality in the sense of (b), the embryo can be described as a developmental being that gives its developmental potential continuously to the next stage ("self-transcendence") and is on the way of becoming a human. This is a reason for defending ethical responsibility for human embryos as the moral recognition of a growing dignity that becomes more intense with increasing proximity to birth.     

Fresh or frozen? Classifying ‘spare’ embryos for donation to human embryonic stem cell research

United Kingdom (UK) funding to build human embryonic stem cell (hESC) derivation labs within assisted conception units (ACU) was intended to facilitate the 'In-vitro fertilisation (IVF)-stem cell interface', including the flow of fresh 'spare' embryos to stem cell labs. However, in the three sites reported on here, which received this funding, most of the embryos used for hESC research came from long term cryopreservation storage and/or outside clinics. In this paper we explore some of the clinical, technical, social and ethical factors that might help to explain this situation. We report from our qualitative study of the ethical frameworks for approaching women/couples for donation of embryos to stem cell research. Members of staff took part in 44 interviews and six ethics discussion groups held at our study sites between February 2008 and October 2009. We focus here on their articulations of social and ethical, as well as scientific, dimensions in the contingent classification of 'spare' embryos, entailing uncertainty, fluidity and naturalisation in classifying work. Social and ethical factors include acknowledging and responding to uncertainty in classifying embryos; retaining 'fluidity' in the grading system to give embryos 'every chance'; tensions between standardisation and variation in enacting a 'fair' grading system; enhancement of patient choice and control, and prevention of regret; and incorporation of patients' values in construction of ethically acceptable embryo 'spareness' ('frozen' embryos, and embryos determined through preimplantation genetic diagnosis (PGD) to be genetically 'affected'). We argue that the success of the 'built moral environment' of ACU with adjoining stem cell laboratories building projects intended to facilitate the 'IVF-stem cell interface' may depend not only on architecture, but also on the part such social and ethical factors play in configuration of embryos as particular kinds of moral work objects.     

In-vitro-Fertilisation und intrazytoplasmatische Spermieninjektion

Since the delivery of the first baby conceived via in vitro fertilization (IVF) in 1978, IVF has become a standard procedure in sterility treatment. In Germany, 78,000 IVF/intracytoplasmic sperm injection (ICSI) cycles are performed annually with a delivery rate per embryo transfer of about 20?%. The cumulative delivery rate after three trials is more than 50?%. The main medical problems are the high rates of multiple pregnancies of more than 20?%, which carry an increased risk for mothers (preeclampsia) and children (preterm delivery, lung immaturity, brain problems). Also singleton babies after IVF are more often too small (small for gestational age, SGA) and delivered preterm. As a result, proper counselling is necessary. New laboratory methods have increased the success rate. Cryopreservation techniques such as vitrification are standard for freezing oocytes, pronuclear-stage oocytes and embryos if they are not needed during the current treatment cycle. Continuous observation of embryos by time-lapse imaging helps to identify the best embryos for transfer. The current legislation in the German embryo protection act (Embryonenschutzgesetz) is the main problem. It is unclear how many fertilized oocytes can be cultured to achieve a transfer of one to three embryos. The prohibition of oocyte donation and surrogacy are not comprehensible from a medical, psychological, and ethical point of view. Reimbursement of publicly insured patients is restricted in comparison with other European countries. Married couples receive half of the payment for three IVF/ICSI cycles; non-married couples receive no payment at all.     

Stem cell research: licit or complicit? Is a medical breakthrough based on embryonic and fetal tissue compatible with Catholic teaching?

In November 1998 biologists announced that they had discovered a way to isolate and preserve human stem cells. Since stem cells are capable of developing into any kind of human tissue or organ, this was a great scientific coup. Researchers envision using the cells to replace damaged organs and to restore tissue destroyed by, for example, Parkinson's disease, diabetes, or even Alzheimer's. But, since stem cells are taken from aborted embryonic and fetal tissue or "leftover" in vitro embryos, their use raises large ethical issues. The National Institutes of Health (NIH) recently decided to fund research employing, not stem cells, but "cell lines" derived from them. The NIH has essentially made an ethical determination, finding sufficient "distance" between cell lines and abortion. Can Catholic universities sponsoring biological research agree with this finding? Probably not. In Catholic teaching, the concept of "complicity" would likely preclude such research. However, Catholic teaching would probably allow research done with stem cells obtained from postpartum placental tissue and from adult bone marrow and tissue. These cells, which lack the pluripotency of embryonic and fetal stem cells, are nevertheless scientifically promising and do not involve the destruction of human life.     

Fresh or frozen? Classifying ‘spare’ embryos for donation to human embryonic stem cell research

United Kingdom (UK) funding to build human embryonic stem cell (hESC) derivation labs within assisted conception units (ACU) was intended to facilitate the ‘In-vitro fertilisation (IVF)-stem cell interface’, including the flow of fresh ‘spare’ embryos to stem cell labs. However, in the three sites reported on here, which received this funding, most of the embryos used for hESC research came from long term cryopreservation storage and/or outside clinics. In this paper we explore some of the clinical, technical, social and ethical factors that might help to explain this situation. We report from our qualitative study of the ethical frameworks for approaching women/couples for donation of embryos to stem cell research. Members of staff took part in 44 interviews and six ethics discussion groups held at our study sites between February 2008 and October 2009. We focus here on their articulations of social and ethical, as well as scientific, dimensions in the contingent classification of ‘spare’ embryos, entailing uncertainty, fluidity and naturalisation in classifying work. Social and ethical factors include acknowledging and responding to uncertainty in classifying embryos; retaining ‘fluidity’ in the grading system to give embryos ‘every chance’; tensions between standardisation and variation in enacting a ‘fair’ grading system; enhancement of patient choice and control, and prevention of regret; and incorporation of patients’ values in construction of ethically acceptable embryo ‘spareness’ (‘frozen’ embryos, and embryos determined through preimplantation genetic diagnosis (PGD) to be genetically ‘affected’). We argue that the success of the ‘built moral environment’ of ACU with adjoining stem cell laboratories building projects intended to facilitate the ‘IVF-stem cell interface’ may depend not only on architecture, but also on the part such social and ethical factors play in configuration of embryos as particular kinds of moral work objects.     

Bioethische und sozialethische Probleme bei der Verwendung von Geweben aus humanen embryonalen Stammzellen sowie der Aufbewahrung von Stammzellen aus dem Nabelschnurblut durch private Firmen zum autologen Gebrauch

The regulation of the European Council and Parliament on advanced therapy medicinal products also includes therapies with human embryonic stem cells. The use of these stem cells is controversially and heavily discussed. Contrary to the use of adult stem cells, medical and ethical problems concerning the use of human embryonic stem cells persists, because this use is based on the destruction of human life at the very beginning. The regulation forsees, therefore, subsidiarity within the European Member States. Although there are no ethical problems in principle with the use of stem cells from the umbilical cord blood, there are social ethical doubts with the banking of these stem cells for autologous use without any currently foreseeable medical advantage by commercial blood banks. Also in this case subsidiarity is valid.     

Social and ethical aspects of in vitro fertilization.

In vitro fertilization (IVF) stands out as one of the contemporary period's most extraordinary technologies, and its social and ethical consequences among the most far reaching. Despite its uncertain effectiveness and medical consequences, IVF has contributed significantly to the medicalization of infertility and the increasingly imperative character of reproductive technology. New developments in IVF, particularly oocyte donation, have created new definitions of treatable infertility and new social needs for IVF; when the technology does not result in pregnancy or healthy babies, these developments have created profound new disappointments. IVF and the commodification of the extracorporeal embryo have also confused the social meaning and legal definition of parenthood. Ultimately the relationship between prospective parents, infertility specialists, and the embryos that they create is a highly ambiguous one. This ambiguity is likely to be a long-term characteristic of efforts to develop, use, and assess assisted reproductive technologies.     

Transfer of only a single embryo in in-vitro fertilisation

In order to obtain high pregnancy rates per IVF cycle, ovarian stimulation is employed to produce multiple embryos. The best embryos are transferred into the uterus and the remainder are frozen for possible use in later cycles. Despite limiting the number of transferred embryos, more than half of all IVF babies are the result of multiple pregnancies. The associated morbidity and costs have led to calls for the adoption of single embryo transfer. New techniques such as pre-implantation genetic screening for aneuploidy have enabled better embryo selection with optimal chances of a healthy child. Milder ovarian stimulation protocols may further reduce the morbidity and costs of IVF cycles. Improved cryopreservation techniques should improve the chances of pregnancies in subsequent cycles using excess embryos. The definition of success in IVF should be changed from number of children per IVF cycle to number of children born after singleton pregnancies per IVF treatment started.     

The derivation and potential use of human embryonic stem cells

Human embryonic stem cells lines can be derived from human blastocysts at high efficiency (>50%) by immunosurgical isolation of the inner cell mass and culture on embryonic fibroblast cell lines. These cells will spontaneously differentiate into all the primary embryonic lineages in vitro and in vivo, but they are unable to form an integrated embryo or body plan by themselves or when combined with trophectoderm cells. They may be directed into a number of specific cell types and this enrichment process requires specific growth factors, cell-surface molecules, matrix molecules and secreted products of other cell types. Embryonic stem (ES) cells are immortal and represent a major potential for cell therapies for regenerative medicine. Their use in transplantation may depend on the formation of a large bank of suitable human leucocyte antigen (HLA) types or the genetic erasure of their HLA expression. Successful transplantation may also require induction of tolerance in recipients and ongoing immune suppression. Although it is possible to customize ES cells by therapeutic cloning or cytoplasmic transfer, it would appear unlikely that these strategies will be used extensively for producing ES cells compatible for transplantation. Embryonic stem cell research may deliver a new pathway for regenerative medicine.     

Derivation characteristics and perspectives for mammalian pluripotential stem cells

Pluripotential stem cells have been derived in mice and primates from preimplantation embryos, postimplantation embryos and bone marrow stroma. Embryonic stem cells established from the inner cell mass of the mouse and human blastocyst can be maintained in an undifferentiated state for a long time by continuous passage on embryonic fibroblasts or in the presence of specific inhibitors of differentiation. Pluripotential stem cells can be induced to differentiate into all the tissues of the body and are able to colonise tissues of interest after transplantation. In mouse models of disease, there are numerous examples of improved tissue function and correction of pathological phenotype. Embryonic stem cells can be derived by nuclear transfer to establish genome-specific cell lines and, in mice, it has been shown that embryonic stem cells are more successfully reprogrammed for development by nuclear transfer than somatic cells. Pluripotential stem cells are a very valuable research resource for the analysis of differentiation pathways, functional genomics, tissue engineering and drug screening. Clinical applications may include both cell therapy and gene therapy for a wide range of tissue injury and degeneration. There is considerable interest in the development of pluripotential stem cell lines in many mammalian species for similar research interests and applications.     

Egg donation for stem cell research: ideas of surplus and deficit in Australian IVF patients' and reproductive donors' accounts

We report on a study undertaken with an Australian in vitro fertilisation (IVF) clinic to understand IVF patients' and reproductive donors' perceptions of oocyte (egg) donation for stem cell research. Such perspectives are particularly valuable because IVF patients form a major recruitment group for oocyte donation for research, and because patients and donors have direct experience of the medical procedures involved. Similar studies of oocyte donation have been carried out elsewhere in the world, but to date very little social science research has been published that reports on donation for research, as distinct from donation for reproduction. Our respondents expressed a distinct unwillingness to donate viable oocytes for stem cell research. In our analysis we consider a number of factors that explain this unwillingness. These include the labour of oocyte production, the inscrutability of oocytes (the lack of a test to identify degrees of fertility) and the extent to which the oocytes' fertility sets the parameters for all downstream reproductive possibilities. We draw on the science studies literature on affordances to make sense of the social intractability of oocytes, and compare them with the respondents' much greater willingness to donate frozen embryos for human embryonic stem cells research.     

干细胞研究进展及相关伦理学问题思考

始于上世纪末,迄今仍方兴未艾的干细胞研究,由于其特殊的细胞分化,组织再生,甚至可能的器官再造特性,引起了又一次生物医学革命,被视为20世纪末最重要的生物医学成就。但同时由于胚胎干细胞涉及的人类胚胎生命及组织、器官的再生成等伦理学问题,干细胞研究从问世的第一天起,就在生物医学家、哲学家、法学家、政治家间引起广泛的争论。文章简要复习了近年来干细胞研究成果及干细胞研究引起的相关伦理学争论,并就干细胞研究引发的伦理学问题及对未来医疗发展的影响提出作者的观点。     

诱导多潜能性干细胞的研究现状与临床应用前景

胚胎干细胞可作为细胞替代治疗中很好的供体细胞来源。但由于伦理学的原因,限制了胚胎干细胞在细胞替代治疗中的应用前景,而诱导多潜能性干细胞(induced pluripotent stem cell,iPS细胞)的出现则提供了一种替代胚胎干细胞的多潜能性细胞。因为iPS细胞的建立不需要卵细胞,也不破坏发育中的胚胎,所以iPS细胞不涉及伦理学问题。而且iPS细胞的建立相对简单,重复性好。因此,iPS细胞在细胞替代治疗和再生医学中有着广泛的应用前景。本文将回顾iPS细胞技术发展的历史,介绍现有的建立iPS细胞的不同方法和评估iPS细胞质量的手段,展望iPS细胞在细胞替代治疗上有待解决的问题和应用前景。     

辅助生殖技术中基因印迹分析

人类辅助生殖临床数据已经显示,辅助生殖技术（ART）与自发流产、早产和围生期死亡、低体质量儿以及一些印迹疾病有关。在配子及胚胎早期发育过程中,基因印迹需经历印迹擦除、重建和维持过程,其中任何一个环节出错都可能导致胚胎发育缺陷,甚至死亡。ART恰施于这一表观遗传重编程的关键时期。因此,这些异常结局可能与ART导致的印迹基因的异常表达有关。而ART中主要的治疗手段有促排卵、体外受精、胞浆内单精子注射（ICSI）和体外培养。这些操作通过干扰基因印迹的重建和维持,影响基因表达和表型,进而影响配子和早期胚胎的发育,从而影响子代的生长发育潜能。