Herzgewebe aus embryonalen Stammzellen

Embryonic stem cells can give rise to all somatic cells, making them an attractive cell source for tissue engineering applications. The propensity of cells to form tissue-like structures in a culture dish has been well documented. We and others made use of this intrinsic property to generate bioartificial heart muscle. First proof-of-concept studies involved immature heart cells mainly from fetal chicken, neonatal rats and mice. They eventually provided evidence that force-generating heart muscle can be engineered in vitro. Recently, the focus shifted to the application of stem cells to eventually enable the generation of human heart muscle and reach following long-term goals: (1) development of a simplified in vitro model of heart muscle development; (2) generation of a human test-bed for drug screening and development; (3) allocation of surrogate heart tissue to myocardial repair applications. This overview will provide the background for cell-based myocardial repair, introduce the main myocardial tissue engineering concepts, discuss the use of embryonic and non-embryonic stem cells, and lays out the potential direct and indirect therapeutic use of human tissue engineered myocardium.     

Embryonale Stammzellen der Maus Eigenschaften, Potenzial und Verwendung

During the last few years research on embryonic stem cells has received much public attention due to the fact that these cells are able to differentiate in vitro into many specialized cells and thus may serve as a source for a variety of tissues. The following article focuses on mouse embryonic stem cells (murine ES cells), because research on these cells has given insight into the potential of embryonic stem cells. Murine ES cells are permanent cell lines established from the inner cell mass (ICM) of early embryos (blastocysts). ES cells are undifferentiated pluripotent cells that are able to undergo an unlimited number of cell divisions without loosing the undifferentiated phenotype. The same is true for mouse primordial germ cell lines (murine EG cell lines), that where established from the fetal progenitor cells of primordial germ cells. Mouse embryonic stem cells are used for different purposes. In basic research they are used to study the consequences of mutations within genes that control embryonic development and/or the development of diseases. Because of their ability to differentiate into a variety of specialized cell types, murine ES cells also serve as model systems to establish specific differentiation protocols. In the last few years protocols were established for the in vitro development of undifferentiated embryonic stem cells into differentiated cardiac, skeletal muscle, neural, adipogenic, haematopoietic, endothelial, chondrogenic or vascular smooth muscle cells. Last but not least, studies on mouse ES cells have demonstrated that embryonic cells and their differentiated derivatives can be used to analyse the effects of toxic substances or of pharmaceutical drugs.     

A European discussion about stem cells for therapeutic use

Stem cells as a source material for growing cellular transplants to repair dysfunctional organs appear to be a new challenge for medical science. Though stem cells are also present in foetal and adult organs, embryonic stem cells from the pre-implantation embryo in particular have the potency to proliferate easily in vitro and the capacity to differentiate into all the body's organ-specific cells. Therefore, these are the ideal cells for developing new cell transplantation therapies for diseases such as Parkinson's disease, diabetes mellitus and heart failure. The use of spare in vitro fertilization (IVF) embryos or pre-implantation embryos specially created to harvest human embryonic stem cells is, however, controversial and an ethical problem. In a European discussion platform organised by the European Commission Research Directorate-General, the status quo of the progress was presented and subsequently commented upon and discussed in terms of medical-ethical, social, industrial and patient interests. The expectations of this new medical technology were high, but clinical trials seem only acceptable once the in vitro differentiation of stem cells can be adequately controlled and once it is known how in vitro prepared stem cells behave after implantation. The ethical justification of the use of in vitro pre-implantation embryos remains controversial. The prevailing view is that the interests of severely ill patients for whom no adequate therapy exists, surmounts the interest of protection of a human in vitro pre-implantation embryo, regardless of whether it was the result of IVF or of transplantation of a somatic cell nucleus of the patient in an enucleated donor egg cell (therapeutic cloning).     

Neonatale Stammzellen

With regard to the great social importance and ethical acceptance of cord blood stem cell research, this article is devoted to basic legal questions concerning the use of umbilical cord blood. The original legal status of the cord blood was analyzed with the result that the cord blood belongs to the child, and thus the child can claim certain personal rights regarding the cord blood. Since the newborn itself is not able to take part in legal transactions, its parents have to ensure that its personal and financial concerns are protected, as they are its legal representatives. The parents can decide together what shall happen to the cord blood because of their parental custody. They have to give their consent to the donation of the cord blood as well as to the collection of personal data of the child. The duty to obtain permission for the production of stem cell preparations derives from the German drug law. Maternity clinics and cord blood banks need this permission and those blood banks that stock up on cord blood stem cell preparations for indefinite recipients have to obtain an additional authorization because these preparations are prefabricated drugs.     

Therapeutic cloning in debate]

Human embryos can be conceived by cell nuclear transfer in order to isolate human embryonic stem cells (hES cells) for research into autologous cell therapy (therapeutic cloning). However, this technique broaches the major ethical problem concerning the instrumental use of human preimplantation embryos. From the viewpoint of subsidiarity, it is argued that various potential alternatives for therapeutic cloning should first be investigated further. The question as to whether therapeutic cloning should be allowed only becomes apparent when research with surplus embryos obtained in the course of in-vitro fertilization suggests that usable transplants can be obtained in vitro from hES cells, and when the potential alternatives for therapeutic cloning are either less promising or need more time for development than is currently expected.     

Humane embryonale Stammzellen

The remarkable capability of human embryonic stem cells (hES cells) to differentiate into all somatic cell types and tissues opens promising perspectives for the development of novel therapeutic approaches for neurological disorders. This article provides an overview on the current state of research in this field. We present strategies and results on the generation of selected neural subtypes (dopaminergic neurons, retinal progenitors, motoneurons, oligodendrocytes) and discuss problems and risks associated with a potential clinical application of this novel cell source.     

Somatische Stammzellen Grundlagen, Konzepte und Herausforderungen

Adult stem cells are multipotent cells that have the ability to self-renew and to differentiate into highly specialized cells. Differentiation of specific cells is not limited to early embryonic development. It also takes place within the adult organism. Adult stem are found in tissues and organs showing a high turn-over rate such as blood, skin or intestine. Moreover, tissues like liver or skin are able to regenerate after injury, indicating the presence of stem cells within these organs. Whereas blood stem cells are already used in transplantation medicine, the biology and therapeutic potential of stem cells isolated from other tissues are still under investigation. Currently, research is focused on the identification and analysis of the factors regulating stem cell self-renewal and differentiation. A better understanding of stem cell biology certainly will lead to new therapeutic concepts, i.e. the use of stem cells and/or their derivatives as replacement cells to treat diseases including for example diabetes, Parkinson's disease, spinal cord injury, stroke, burns, rheumatoid arthritis.     

Forschen mit humanen embryonalen Stammzellen in Deutschland

From July 2002 to May 2008, 36 applications for the import and use of human embryonic stem cells (hES) were reviewed by the German Central Ethics Committee for Stem Cell Research (ZES). A flood of applications anticipated by opponents to human embryonic stem cell research has not occurred since the enactment of the German Stem Cell Act in 2002. On the contrary, German hES cell research is below international average in terms of project numbers. The current restrictions for using hES cells in Germany might be causative for the opinion that this type of research is not considered to be very promising. This could hold true especially for research aiming at clinical applications. Consequently, potential research goals of premium importance, especially those of potential clinical relevance, could be seriously jeopardized.     

Regulatorische Aspekte der Anwendung humaner Stammzellen

Human stem cells can be the active ingredient of medicinal products for somatic cell therapy or may be used as the starting or source material for their manufacture. The regulations covering pre-clinical and clinical studies in Germany involving the use of somatic cell therapy drugs, which are medicinal products according to §2 of the German Drug Law (AMG; Arzneimittelgesetz), are defined in the AMG and allow rapid initiation of manufacture and clinical trials. “Points to Consider on the manufacture and quality control of human somatic cell therapy medicinal products (CPMP/BWP/41450/98)” were published by the “Biotechnology Working Party” at the European Agency for the Evaluation of Medicinal Products (EMEA). Although somatic cell therapy drugs will mostly be used as individually prepared medicinal products, clinical trials seem suitable for an objective analysis of the safety and efficacy of these drugs. The transformation of the so-called Good Clinical Practice (GCP)-Directive into German drug regulations, which is currently being considered, will involve the introduction of an approval of clinical trials by a competent authority. Currently, the positive appraisal of the competent local ethics committee is of main relevance for the initiation of clinical trials. If individually prepared somatic cell therapy drugs will be industrially manufactured, obtaining marketing authorisation via the EMEA may be considered in the future.     

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。     

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.     

Ethical Aspects of the Use of Stem Cell Derived Gametes for Reproduction

A lot of interest has been generated by the possibility of deriving gametes from embryonic stem cells and bone marrow stem cells. These stem cell derived gametes may become useful for research and for the treatment of infertility. In this article we consider prospectively the ethical issues that will arise if stem cell derived gametes are used in the clinic, making a distinction between concerns that only apply to embryonic stem cell derived gametes and concerns that are also relevant for gametes derived from adult stem cells. At present, it appears preferable to use non-embryonic stem cells for the derivation of gametes. Adult stem cell derived gametes do not present any problems with regard to the moral status of the human embryo, bypass the safety risks linked to SCNT and do not present any ambiguity or novel problems with regard to informed consent, psychological consequences for the child or genetic parenthood. A remaining ethical concern, however, regards the safety of the procedure in terms of the welfare of the resulting children. This should spark a thorough reflection on how far one must go to accommodate a person’s wish to have a genetically related child.     

Somatische Stammzellen des zentralen Nervensystems

During neural development, the nervous system is created from stem cells that have the potential to proliferate, to reproduce (self-renew) themselves, and to differentiate into the appropriate neuronal and glial phenotypes. Although the adult brain has traditionally been thought of as a structure with very limited regenerative capacity, these neural stem cells have recently been shown to exist in the adult central nervous system (CNS) as well. In vitro and following transplantation, neural stem cells obtained from the fetal and adult brain are able to generate neurons, astrocytes, and oligodendrocytes, the three major CNS cell types. Therefore, neural stem cells are potential sources for specialized neural cells needed to treat a variety of neurological disorder. The present review describes how somatic stem cells of the central nervous system can be cultivated in vitro and to which extend stem cell transplantation is effective in animal models for neurological diseases. Finally, a perspective is given on the potential clinical use of human neural stem cells for the treatment of neurological diseases.     

Differentiation of embryonic and adult stem cells into insulin producing cells

Replacement of insulin producing cells represents an almost ideal treatment for patients with diabetes mellitus type 1. Transplantation of pancreatic islets of Langerhans is successful in experienced centers. The wider application of this therapy, however, is limited by the lack of donor organs. Insulin producing cells generated from stem cells represent an attractive alternative. Stem cells with the potential to differentiate into insulin producing cells include embryonic stem cells (ESC) as well as adult stem cells from various tissues including the pancreas, liver, bone marrow and adipose tissue. The use of human ESC is hampered by ethical concerns but research with human ESC may help us to decipher important steps in the differentiation process in vitro since almost all information available on pancreas development are based on animal studies. The present review summarizes the current knowledge on the development of insulin producing cells from embryonic and adult stem cells with special emphasis on pancreatic, hepatic and human mesenchymal stem cells.     

Die Kriterien der Hochrangigkeit, der hinreichenden Vorklärung und der „Alternativlosigkeit“ nach § 5 Stammzellgesetz aus ethischer Sicht

The German Stem Cell Act forbids, in principle, the importation und use of human embryonic stem cells, but provides for exceptions under specific conditions. It is the first Federal German law that grants an ethical review authority over the approval process. The legislature has indeed established the criteria for the work of the members of the "Central Ethics Commission for Stem Cell Research" appointed by the Federal Government. The three criteria include the following: 'high priority of the research goals', sufficiencyy of research in the animal and adult human models' and 'the absence of an alternative'. Together they legitimate the importation and use of human embryonic stem cells. This paper seeks to elucidate these three criteria, to analyze their dual function as ethical and as scientific concepts, and to illustrate the ways in which they are being used.     

Ethics, politics, and human embryo stem cell research.

Three reports on ethical aspects of research involving human embryonic stem cells were issued in the final months of 1999. Two were from governmental agencies or commissions: the National Institutes of Health and the National Bioethics Advisory Commission. The third report was issued by the American Association for the Advancement of Science and the Institute for Civil Society. All three reports endorse the use of federal funds for embryonic stem cell research, but other differences distinguish these reports. This article describes the differences and provides an ethical analysis of the main arguments.     

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.     

An Ethical Framework for Stem Cell Research in the European Union

The European Union is a nightmare from the perspective of the ethics and regulation of science. A hitherto insoluble problem has been the task of drafting ethical principles which do not founder on the radically different attitudes taken to the question of the moral status of the human embryo. Following the conclusions reached in an international project, EUROSTEM, we suggest that this problem can be solved by concentration on the scope of principles and we emphasize that European research should be funded in a way that does not discriminate between individual states and researchers in the EU. Finally, we observe that the availability of any eventual embryonic stem cell therapies will pose a dilemma for those countries and those people that have declared stem cell research to be unacceptable.