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The Spanish National Stem Cell Bank (Banco Nacional de Líneas Celulares, BNLC) was established in 2006 thanks to a change in the legislative framework in Spain. The Law 14/2006 updated the previous Assisted Reproduction Techniques Law (Law 45/2003) allowing the use of the surplus frozen embryos following IVF for research. The BNLC has a network structure with 3 nodes: the Regenerative Medicine Program (IDIBELL), the Principe Felipe Research Center (CIPF) in Valencia and the Andalusian Public Health System Biobank (SSPA Biobank) in Granada. The aim of the BNLC is to guarantee throughout the national territory the availability of human stem cell lines for biomedical research. At present time, there are 40 human embryonic stem cell lines (hESC) and 171 human induced pluripotent stem cell lines (hiPSC) registered in the BNLC. These lines are fully characterized and available in the context of research projects approved by the Technical Committee of the BNLC. The National Spanish Stem Cell Bank is supported by the Plataforma de Proteomica, Genotipado y Líneas Celulares (PT1770019/0015) (PRB3), Instituto de Salud Carlos III. Sí

Synthetic embryology endeavors to use stem cells to recapitulate the first steps of mammalian development that define the body axes and first stages of fate assignment. Well-engineered synthetic systems provide an unparalleled assay to disentangle and quantify the contributions of individual tissues as well as the molecular components driving embryogenesis. Experiments using a mixture of mouse embryonic and extra-embryonic stem cell lines show a surprising degree of self-organization akin to certain milestones in the development of intact mouse embryos. To further advance the field and extend the mouse results to human, it is crucial to develop a better control of the assembly process as well as to establish a deeper understanding of the developmental state and potency of cells used in experiments at each step of the process. We review recent advances in the derivation of embryonic and extraembryonic stem cells, and we highlight recent efforts in reconstructing the structural and signaling aspects of embryogenesis in three-dimensional tissue cultures.

The first French clinical trial using human embryonic stem cells for regenerative purposes was launched in 2014, using the I6 stem cell line that was imported from Israel. From Israel to France, national reproductive policies and practices inform how basic scientists produce, manage and circulate cells across countries. Building on an interdisciplinary co-production involving two social scientists and a life scientist, this article suggests that biobanks passage cells from in vitro fertilization to stem cell science and from country to country by modifying their reproductive meaning. Four passages are described: the absence of cells in 2005 when the research started in France; the presence of supernumerary embryos available for research in Israeli IVF biobanks; the production of the I6 stem cell bank in Israel; the importation and laboratory biobanking of the cells in France. Human embryonic stem cell lines can never be completely disentangled from reproduction.

Haploid genetics has facilitated new insights into mammalian pathways and disease mechanisms. Most animal cells are diploid, and mammalian haploid cell cultures have remained elusive for a long time. Recent methodological progress has enabled the routine derivation of haploid stem cell lines from mammalian haploid embryos. Here we provide detailed protocols for the establishment, culture, and manipulation of parthenogenetic and androgenetic haploid embryonic stem cells from mouse embryos.

Stem cells (SCs) are thought to have great therapeutic potential, but due to continuously and stochastically arising new mutations that unpredictably change the composition of a cell population, the large-scale manufacturing of SCs with uniform properties and predictable behavior is a challenge. Quantitative evaluation of the characteristic mutation rate of a given stem cell line could be an important criterion in making the decision to use the line in medical practice. Such an evaluation could provide a new quality standard for newly derived human embryonic stem cell (hESC) lines prior to depositing them in stem cell banks. Here, we substantiate this view with simple calculations showing the effect of the mutation rate on changes in the cell population composition due to amplification. Selection of SCs with low mutation rate could reduce the risk of negative side effects during treatment.

Notable distinctions between an embryonic stem cell (ESC) and somatic cell are that an ESC can maintain an undifferentiated state indefinitely, self-renew, and is pluripotent, meaning that the ESC can potentially generate cells representing all the three primordial germ layers and contribute to the terminally differentiated cells of a conceptus. These attributes make the ESC an ideal source for genome editing for both agricultural and biomedical applications. Although, ESC lines have been successfully established from rodents and primates, authentic ungulate stem cell lines on the contrary are still not available. Outstanding issues including but not limited to differences in pluripotency characteristics among the existing ESC lines, pre-implantation embryo development, pluripotency pathways, and culture conditions plague our efforts to establish authentic ESC lines from farm animals. In this review, we highlight some of these issues and discuss how the recent derivation of induced pluripotent stem cells (iPSCs) might augur the establishment of robust authentic ESC lines from farm animals.

Exposition of best practice in management and experimental use of human stem cell lines in radiobiological research. This paper outlines the key challenges to be addressed by radiobiologists wishing to use human pluripotent stem cell (hPSC) lines in their research including human embryonic stem cell (hESC) lines and human induced pluirpotency stem (hiPSC) lines. It emphasises the importance of guidance already established for cell culture in general and outlines some further considerations specific to the culture of human pluripotent stem cell lines which may impact on the interpretation of data from radiobiological studies using these cells. Fundamental standards include obtaining cells from bona fide suppliers with suitable quality controls, screening cell lines to ensure absence of mycoplasma and authentication of cell lines by DNA profiling. For hESC and hiPSC lines, it is particularly important to recognise the significance of phenotypic and genetic stability and this paper will address approaches to reduce their impact. Quality assured banking of these two types of stem cell lines will facilitate reliable supply of quality controlled cells that can provide standardisation between laboratories and in the same laboratory over time.hPSC lines could play an important role in future radiobiological research providing certain fundamental principles of good stem cell culture practice are adopted at the outset of such work.

Whereas conservative therapies aim to stall the advance of disease, regenerative medicine strives to reverse it. The capacity of most tissues to regenerate derives from stem cells, but there are a number of barriers which have to be circumvented before it will be possible to use stem-cell-based therapies. Such therapies, however, are expected to improve human health enormously, and knowledge gained from studying stem cells in culture and in model organisms is now laying the groundwork for a new era of regenerative medicine. One of the most prominent methods to study stem cell differentiation is to let them to form embryoid bodies. Under favourable conditions any stem cell line will form embryoid bodies. However, the mechanism of the formation of embryoid bodies is not very well understood, and to produce them in the laboratory is in no way trivial – an important technical barrier in stem cell research. Recently, the embryoid body cultivation step has been successfully circumvented for the derivation of osteogenic cultures of embryonic stem cells. Here we report on a simple and reusable system to cultivate embryoid bodies in extremely short times. The method is inspired by the principles that lead to the establishment of the biomimetic triangle.

Stamselnavorsing is 'n asemrowende tegnologie waar die mens se eie selle gebruik word om genesing te bewerk. Stamselle is spesiale selle wat die vermoë het om tot enige sel in die liggaam te ontwikkel en defektiewe selle te herstel of te vervang. Navorsers het stamselle uit die menslike (en dierlike) embrio, fetus, naelstring en volwasse liggaam geïsoleer en tot stamsellyne voorberei vir terapie. Verbasende resultate is alreeds aangetoon. In sommige gevalle het navorsers ten volle genesing bewerk of ten minste groot verbeter tot stand gebring in diere (en in enkele gevalle by mense) met suikersiekte, Parkinson en Alzheimer se siektes en outo-immuunsiektes. Die gebreekte rugmurg van rotte is ook al deur hierdie tegnologie herstel. Die doel van hierdie artikel is om oorsigtelik aan die tegniese uitvoerbaarheid en vordering in stamselnavorsing aandag te gee. Uit hierdie gegewens sal dit duidelik word dat daar heelwat algemene en tegniese probleme met meegaande etiese implikasies bestaan, wat eers opgelos moet word voordat hierdie terapie bruikbaar sal wees. Probleme wat geïdentifiseer is, is die noodwendige vernietiging van die menslike embrio, die oorweging van terapeutiese kloning, plasing van menslike embrionale stamselle in embrio's van primate soos ape en 'n reeks tegniese probleme in die ontwikkeling van stamsel-tegnologie. Stem cell research is a breathtaking technology where man's own cells are used to effect a cure for certain ailments. Stem cells are specially developed cells that contain the ability to develop into any cell in the body and to cure or replace defective cells. Researchers isolated stem cells from the human (and animal) embryo, foetus, umbilical cord, and adult body and developed them to stem cell lines for therapy. Astonishing results have already been shown. In some instances researchers achieved full cure or at least huge improvement in animals (and in a few instances with human beings) with diabetes, Parkinson's and Alzheimer's diseases and auto-immune diseases. The broken spinal marrow ofrats has also been repaired through this technique. The aim of this article is to give an overview of the technical feasibility and advancement of this field of research. It will become apparent from these facts that there are a large number of general and technical problems with the accompanying ethical implications, that will have to be resolved before this therapy can be applied. Problems that have been identified include the necessary destruction of the human embryo, the consideration of therapeutic cloning, the placing of human embryonic cells in embryos of primates such as apes and a series of technical problems in the development of stem cell technology.

Congenital anomalies are a significant burden on human health. Understanding the developmental origins of such anomalies is key to developing potential therapies. The Human Developmental Biology Resource (HDBR), based in London and Newcastle, UK, was established to provide embryonic and fetal material for a variety of human studies ranging from single gene expression analysis to large-scale genomic/transcriptomic studies. Increasingly, HDBR material is enabling the derivation of stem cell lines and contributing towards developments in tissue engineering. Use of the HDBR and other fetal tissue resources discussed here will contribute to the long-term aims of understanding the causation and pathogenesis of congenital anomalies, and developing new methods for their treatment and prevention.

In 2009 the International Stem Cell Banking Initiative (ISCBI) contributors and the Ethics Working Party of the International Stem Cell Forum published a consensus on principles of best practice for the procurement, cell banking, testing and distribution of human embryonic stem cell (hESC) lines for research purposes [1] , which was broadly also applicable to human induced pluripotent stem cell (hiPSC) lines. Here, we revisit this guidance to consider what the requirements would be for delivery of the early seed stocks of stem cell lines intended for clinical applications. The term 'seed stock' is used here to describe those cryopreserved stocks of cells established early in the passage history of a pluripotent stem cell line in the lab that derived the line or a stem cell bank, hereafter called the 'repository'. The seed stocks should provide cells with suitable documentation and provenance that would enable them to be taken forward for development in human therapeutic applications. WHO recommendations for the evaluation of animal cell cultures as substrates for the manufacture of biologicals and for the characterization of cell banks were updated in 2010 and provide a number of definitions and guiding principles that may apply to stem cells. The term 'cell bank' is used to describe a stock of vials or other containers of cells with consistent composition aliquoted from a single pool of cells of the same culture history (for other specific definitions see PAS 84 [2] and WHO [3] ).Three important assumptions have been made in the preparation of this document. First, that seed stocks of hPSCs are used as starting materials to make cell banks for use in clinical trials. The cell banks made within a clinical trial would need to be established according to Good Manufacturing Practice (GMP) in a facility with a relevant product manufacturing license. These banks would need additional risk assessment focused on the new banking process/reagents and the specific intended clinical application. Second, it has been assumed that undifferentiated pluripotent stem cells would not be inoculated into patients. Third, where feeder cells are used to culture hPSC lines, their cellular nature and intimate contact with the therapeutic cells means that they should be subject to similar risk assessment and banking procedures as applied to the hPSC cells.It is important to note that responsibility for establishing and updating national regulations for medicinal products relies on National Regulatory Authorities. Therefore, national requirements for cell therapy may vary considerably. Accordingly, it is not intended that this international consensus provides comprehensive guidance that will ensure compliance with requirements in any given jurisdiction. Rather, it is designed to aid the development of clinical grade materials by providing points to consider in the preparation of seed stocks of stem cell lines for use in cell therapy. It may arise that there are circumstances where it is not reasonably possible to meet specific procedures presented in this document. Where this is the case any alternative procedures should be justified and mitigate against any adverse consequences. Finally, this document could also serve as a useful reference to assist in the evaluation of potential sources of candidate cell lines for the development of cell-based medicines, and provide the links necessary to identify some of the key differences in regulatory requirements between countries.

In this paper I analyse who should be able to control the use of human embryonic stem cell lines. I distinguish between different kinds of control and analyse a set of arguments that purport to show that the donors of gametes and embryos should not be able to control the use of stem cell lines derived from their embryos. I show these arguments to be either deficient or of so general a scope that they apply not only to donors but also to those who derived the stem cell lines. Since we normally think that stem cell derivers have the right to control the use of the cell lines they derived, we have no justification for denying donors similar rights of control. In the final section I briefly discuss why informed consent is not an appropriate vehicle for transferring or alienating control rights.

The rapidly expanding field of stem cell research offers the potential to develop therapeutic agents to treat diseases such as Parkinson's, diabetes and heart disease. It is important that stem cell lines derived from quality-controlled and well-characterised cell banks should be made available to both the scientific and clinical communities to promote high-quality research and development. The requirement in the United Kingdom (UK) for rigorous regulation of the procurement and use of embryonic stem (ES) cell lines led the UK government to fund the establishment of a national bank for stem cell lines. The UK Stem Cell Bank (UKSCB) hosted at the National Institute for Biological Standards and Control (NIBSC) is committed to working closely with the clinical and research communities to provide qualified stocks of human stem cell lines of adult, foetal and embryonic origin for both research use and for use in emerging human therapy.

In February 2004, South Korean researchers became the first in the world to successfully harvest stem cells and establish a stem cell line from a cloned human embryo. This is just one of eight possible policy options concern- ing human embryonic stem cell research. In practice, every kind of stem cell research can be done in one country or another. This paper evaluates the eight policy options concerning human embryonic stem cell research in light of the arguments and decisions behind them. Stem cells are truly remarkable. They bridge the gulf between the fertilized egg that is our origin and the architecture that we become. They supply the cells that construct our adult bodies and, as we age, replenish worn out, damaged and diseased tissues. They renew themselves, resisting the power- ful pull towards differentiation that overcomes more prosaic cells. And depending on the source, they have the potential to form one, many or all cell types of an organism. (DeWitt 2001, p. 87)

Yaffe and colleagues discuss the issues surrounding the authentication and quality of induced pluripotent stem cells.

International audience; The burden of neurodegenerative disorders in an aging population has become a challenge for the modern world. While the biomarkers available and the methods of diagnosis have improved to detect the onset of these diseases at early stages, the question of adapted and efficient therapies is still a major issue. The prospect of replacing the loss of functional neural cells remains an attractive but still audacious approach. A huge progress has been made in the generation of neurons derived from human stem cell lines and transplantation assays are tested in animals for a wide range of pathologies of the central nervous system. Here we take one step back and examine neuronal differentiation and the characterization of neural progenitors derived from human embryonic stem cells. We gather results from our previous studies and present a cell model that was successfully used in functional analyses and engraftment experiments. These neuronal precursors exhibit spontaneous and evoked activity, indicating that their electrophysiological and calcium handling properties are similar to those of matured neurons. Hence this summarized information will serve as a basis to design better stem cell-based therapies to improve neural regeneration.

The successful exploitation of human cells for research, translational, therapeutic, and commercial purposes requires that effective and simple cryopreservation methods be applied for storage in local and master cell banks. Of all the cell types utilized in modern research, human embryonic stem cells and their more recent relatives, induced pluripotent stem cells, are two of the most sensitive to cryopreservation. It is frequently observed that the lack of quality control and proper processing techniques yield poor recovery of pluripotent stem cells. The procedures in this unit have been optimized for handling some of the most recalcitrant stem cell lines, and provide a method for controlled-rate freezing, using minimal equipment that affords levels of cell viability comparable to expensive controlled-rate freezers. The protocol also eliminates the requirement for isopropanol, avoiding the hazards, on-going cost, and inconsistencies associated with its use and disposal. It provides a clinically relevant, inexpensive, reliable, and user-friendly method that successfully prepares cells for long-term cold storage and ensures maximum levels of cell viability post thaw.

Pluripotent stem cells from the early embryos, the embryonic stem cells (ESC), have been the subject of intensive investigation for the past two decades. Much of the excitement surrounding ESC research has been centered on the potential of ESC in differentiating into target cell types, disease modeling, and in offering cures for intractable diseases. So far, rodents and primates are the only species from which “bonafide” ESC have been readily established and have met relatively stringent criteria of pluripotency. However, attempts to generate analogous pluripotent stem cells from other relevant domestic ungulates have been unsuccessful. While the reasons for poor outcome still remain a focus of active investigation, the establishment of induced pluripotent stem cells (iPSC) from somatic cells by upregulation of select few reprogramming factors has emerged as an attractive option. In the last few years since the inception, the iPSC field has witnessed substantial progress, with iPSC established from every major large animal species. The iPSC are playing an important role in understanding species-specific differences in pluripotency, unique requirements for their in vitro culture, and in achieving scientific and technical progress towards the establishment of authentic stem cell lines. These topics will be illustrated and discussed in detail in this chapter.

In this research, we examine how restrictive policy influenced performance in human embryonic stem cell research (hESC) between 1998 and 2008. In previous research, researchers argued whether restrictive policy decreased the performance of stem cell research in some nations, especially in the US. Here, we hypothesize that this policy influenced specific subfields of the hESC research. To investigate the selective policy effects, we categorize hESC research publications into three subfields—derivation, differentiation, and medical application research. Our analysis shows that restrictive policy had different effects on different subfields. In general, the US outperformed in overall hESC research throughout these periods. In the derivation of hESC, however, the US almost lost its competence under restrictive policy. Interestingly, the US scientific community showed prominent resilience in hESC research through international collaboration. We concluded that the US resilience and performance stemmed from the wide breadth of research portfolio of US scientists across the hESC subfields, combined with their strategic efforts to collaborate internationally on derivation research.

Delivery of human stem cells for research, clinical translation, and commercialization ideally requires stem cell resources developed and maintained according to internationally recognized standards. For example, human embryonic stem (hES) cells and induced pluripotent stem (iPS) cells should conform to international ethical principles imparted by leading bodies such as the International Society of Stem Cell Research (ISSCR; www.isscr.org), International Stem Cell Forum (ISCF; www.stem-cell-forum.net), and U.S. National Academy of Sciences (USNAS; www.nasonline.org), and be quality-controlled based on principles of best-practice for manufacture, culture, characterization, storage, distribution, and translation. The International Stem Cell Banking Initiative (ISCBI) has taken the lead in defining such principles so as to standardize current and future practices that are essential to good scientific practice and clinical use through regulatory and public approval. This chapter considers the importance of standardizing stem cell banking and the central role of ISCBI as a major proponent of coordinated hES and iPS cell banking.

Stem cells’ regenerative capabilities present a unique opportunity to treat human illness and injury. In 2003, the National Society of Genetic Counselors (NSGC) issued a position statement supporting stem cell use in research settings. Almost a decade later, in response to legislative and technological developments within the field of stem cell science, NSGC convened a task force to revisit and update its statement on stem cell research. In doing so, the Task Force developed a new statement reaffirming NSGC’s support for stem cell research and endorsed continued stem cell therapy development. NSGC recognizes that the unique potential of stem cell therapy to treat human disease and injury can be realized only through research on a diverse array of stem cell lines drawn from multiple sources, including embryonic, cord blood, and adult cells. NSGC supports the use of stem cells in research and clinical settings when practices adhere to defined ethical and legal guidelines. Available stem cell lines should reflect our genetically diverse population, and donor recruitment should be without discrimination or coercion and include a thorough and dynamic informed consent process.

PLoS one 8(1), e52068 (2013). doi:10.1371/journal.pone.0052068, Published by PLoS ; [S.l.] : PubMed Central [u.a.], Lawrence, Kan.

Human embryonic stem cell lines have the capability to develop into cells representative of the three germ layers of the human body, which has raised the possibility of exciting new opportunities for in vitro research and the development of therapies for the future. However, it is vital that in these pursuits researchers are aware of certain critical issues in sourcing cell lines to ensure that their work provides data of a high standard and does not lead to confusion and that any future use of the cells – such as clinical application – is not compromised by the conditions under which the cells are developed. Stem cell banks have been much discussed in the literature and would appear to have a significant role to play in this important area of endeavour. This chapter places the current development of stem cell banking against the history of bioresource centres and culture collections. It also identifies the different types and roles that stem cell banks may have and as a case study describes the particular remit of the UK Stem Cell Bank and how this influences its policies and procedures. The author goes on to explain the importance of careful development of cell line procurement procedures, the need for standardised banking protocols and the challenges for appropriate supply of pluripotent stem cell lines. In conclusion, the author outlines the importance of international collaboration between the developing network of stem cell banks giving examples of standards (e.g. www.stemcellfoum.org/) that may develop from such activity.

The work on human embryonic stem cells is being performed with a variety of cell lines using a variety of culture conditions; a situation that makes standardisation between projects and publications very difficult. Clearly the consequence of using such cells would be wasted time and resources but, more seriously, the generation of erroneous data in the literature which could both confuse and delay scientific progress in this area. This guidance document represents the outcome of the first meeting of the group named The International Stem Cell Banking Initiative held in October 2007. The document has been prepared from the perspective of hESC culture but, in many respects, is broadly applicable to all human stem cell lines including induced pluripotent stem cell lines.

An increasingly unbridgeable gap exists between the supply and demand of transplantable organs. Human embryonic stem cell technology could solve the organ shortage problem by restoring diseased or damaged tissue across a range of common conditions. However, such technology faces several largely ignored immunological challenges in delivering cell lines to large populations. We address some of these challenges and argue in favor of encouraging contribution or intentional creation of embryos from which widely immunocompatible stem cell lines could be derived. Further, we argue that current immunological constraints in tissue transplantation demand the creation of a global stem cell bank, which may hold particular promise for minority populations and other sub-groups currently marginalized from organ procurement and allocation systems. Finally, we conclude by offering a number of practical and ethically oriented recommendations for constructing a human embryonic stem cell bank that we hope will help solve the ongoing organ shortage problem.

Research with human embryonic stem cells (hESCs) has been controversial, but in the seven years since their isolation by James Thomson [1], governments have largely answered, at least for now, the first-level questions about this research. We now know in most jurisdictions whether derivation of hESC lines will not be permitted from any embryos or whether it will be permitted from all embryos, only from embryos created as part of in vitro fertilization clinical services (IVF), or only from embryos not created by somatic cell nuclear transfer (SCNT). We also have learned where the various kinds of cell lines, if derived elsewhere, may be used, and whether public funding for the derivation or use of some or all of the lines will be possible. A set of second-level questions, revolving around the donors of cells and embryos used in this research, is also rapidly being answered.

Current U.S. policy on human embryonic stem cell (hESC) lines is a dual-track policy. About 20 lines derived from the 70 derivations undertaken before August 9, 2001, are available (and in sufficient quantities) such that basic researchers can obtain them for research studies. Research projects using these lines are eligible for federal funding, and the bulk of research reports published have used these cell lines. Despite their overall similarity in selfrenewal, expression of markers, and ability to differentiate, certain differences among these lines have also been reported. These include differences in growth rates, ability to form rosettes, gene methylation patterns, karyotypic stability, polymorphisms, and changes associated with long-term propagation in culture. In the last few years, a host of additional hESC lines have been generated. These include cell lines derived at different stages of early embryonic development, lines derived using different methods of isolation, and lines derived from embryos carrying a known genetic defect or generated via somatic cell nuclear transfer. Although it is legal to work on these lines in the U.S., the infrastructure for large-scale characterization of stem cell lines developed over many years involving NIH and other federal support cannot currently be used to characterize these lines. Given the numbers of new hESC lines that continue to become available, the lower cost to obtain them (free for many derived post-August 9, 2001, vs. more than $5,000 for most lines that predate that time), and their diversity and other qualitative advantages, it is likely that many of the new cell lines will be studied, perhaps by different investigators.

German embryonic stem cell scientist Oliver Brustle faces major challenges in his lab on a daily basis that have little to do with science. His country's policy on human embryonic stem cells (hESCs) is among the most restrictive in Europe. Collaborations with other countries are difficult. And he's overwhelmed by the time and paperwork necessary to comply with regulations and to apply for permits.

The US National Academy of Sciences has published guidelines to advance the science of stem cell research “in a responsible manner.” The report calls for each US institution conducting stem cell research to establish a committee on embryonic stem cell research that would oversee all the issues relating to the derivation and use of stem cell lines. Such heightened oversight is essential, the report says, to assure the public that research is …

Ethical and regulatory issues concerning embryonic stem (ES) cell research are reviewed here a year after the controversy became a public and political issue in the US. The background of various issues are examined and the current regulations in various countries are reviewed. In the US, the debate is linked with abortion, as well as the status of a fetus as a human being, and is politically driven. Obtaining stem cells from embryonic tissues involves destruction of the embryo, to which objections are raised. Religious beliefs are examined and no serious impediments to ES cell research could be identified. Regulations vary from one country to another and it is unlikely that there will ever be any universally uniform ethical and regulatory standards for ES cell research. Currently, the most liberal and favourable environments for ES cell research are in the UK, Singapore, Sweden, India, Israel and China. Unless the US liberalises ES cell research, it may lose its lead in ES cell research and investments in this area may drift to countries with better environments for research. Suggestions are offered in this review to improve the ethical environment for ES cell research.

In Canada it is permissible to proceed with stem cell research using human embryos created by in vitro fertilization (IVF) provided: these were originally created for infertility treatment; they are no longer required for such treatment; and there is an appropriate consent for their research use. As such, IVF human embryos in excess of clinical need are a valuable resource for embryonic stem cell researchers. A point often overlooked, however, is that these excess IVF human embryos are also a scarce resource. Their scarcity suggests the need to develop sound policies and procedures, in a timely and coordinated fashion, to ensure that the few human embryos available for embryonic stem cell research are not used in less important research endeavours or used when other biological materials are appropriate. Injudicious use of the few human embryos available for research use may risk the following consequences: no ongoing research in Canada to derive human embryonic stem cell lines; a reliance on the importation of stem cell lines from other countries for any research on the use of embryonic stem cells; and pressure from Canadian researchers to remove the prohibition on the purposeful creation of human embryos for research use.

In 2001, the U.S. House of Representatives passed the "Human Cloning Prohibition Act" and President Bush announced his decision to allow only limited research on existing stem cell lines but not on "embryos." In contrast, the U.K. has explicitly authorized "therapeutic cloning." Much more will be said about bioethical, legal, and social implications, but subtleties of the science and careful definitions of terms have received much less consideration. Legislators and reporters struggle to discuss "cloning," "pluripotency," "stem cells," and "embryos," and whether "adult" are preferable to "embryonic" stem cells as research subjects. They profess to abhor "copying humans" or "killing embryos." Do they know what they are talking about? Do we? This paper explores the historical, philosophical, and scientific contexts that inform this heated discussion.

The Bush administration conceded that only about 25 embryonic stem cell lines are fully developed, a sharp change from its earlier assertion that more than 60 such lines are available worldwide for federally funded research and ready for use. The concession came during testimony delivered by the secretary of health and human services, Tommy Thompson, before a congressional committee this week. In particular, Mr Thompson backed off earlier pronouncements that all 64 groups of cells were “robust, viable” embryonic stem cell lines. Instead, he said that the administration had identified “64 derivations” of which “24 or 25” are fully developed into usable cell lines. …

Human therapeutic cloning is a recently emerged application of somatic cell nuclear transfer (SCNT), which is currently being performed to produce patient-specific stem cell lines for future stem cell therapies. The advantages in producing human nuclear transfer (NT) embryos to derive NT stem cell lines are that these can be tailor-made (i.e., are autologous in nature) for the patient and may overcome the need to administer life-long immunosuppression following stem cell transplantation. Although the rationale for using NT embryos is not for reproductive purposes, human NT remains clouded in ethical, moral, and religious controversies. The recent retraction of high-impact factor publications in the field of human NT from a research group in South Korea has placed stem cell research in a delicate situation. These heavily publicized issues may hinder the progress of this research and may threaten to bring current research to a complete halt. This review outlines the recent status of human NT, its continuing progress and the difficulties the field faces. Of most concern are the ethical issues, which surround obtaining human oocytes for research. Recent evidence suggests that failed-to-fertilize oocytes are poor sources for human SCNT, but obtaining fresh, viable oocytes may be even more problematic. The current status of human SCNT is outlined in this review with particular reference made to, lessons learnt from animal research, the oocyte dilemma and optimization of human NT.

Although human and mouse embryonic stem cells share many characteristics, their behaviors are not identical. Two recent papers describe the derivation of stem cell lines from mouse epiblast that may provide an explanation for the unique character of human embryonic stem cells.

WHEN IT COMES TO doing research with human embryonic stem cells, U.S. scientists face many hurdles. The most prominent of these maybe current U.S. policy, which strictly limits the stem cell lines ...

Evaluation of: Chung Y, Klimanskaya I, Becker S et al.: Embryonic and extra-embryonic stem cell lines derived from single mouse blastomere. Nature Epub ahead of publication Oct 16, Letters, 1–4 (2005).

BIOTECHNOLOGYThe stock market slump and subsequent evaporation of venture capital is being felt keenly across the biotech landscape. Hit particularly hard is one of the hottest areas of all: human embryonic stem cells and therapeutic cloning, the creation of stem cell lines that are identical genetically to a prospective patient's. The depth of suffering among stem cell companies reflects how far off profits may lie.

STEM CELLSBONN-- Germany's main research funding agency issued new guidelines last week paving the way for researchers to import human embryonic stem cells from other countries. The Deutsche Forschungsgemeinschaft also recommended that Parliament pass a law, if needed, that would allow German researchers to derive their own stem cell lines from surplus embryos from in vitro fertilization clinics.

The article presents questions and answers related to embryonic stem cell lines including where the embryos used for stem cell lines come from, the number of stem cell lines that exist, and why the amount that exist is not enough.

any scientists and patient advocates cheered earlier this summer when the National Institutes of Health (NIH) released new guidelines for human embryonic stem cell (hESC) research. The guidelines came after President Obama’s March 2009 executive order lifting the restrictions on federal support for research using embryonic stem cells. Obama’s directive revoked the Bush administration’s restrictions and funding ban on hESC research, which had limited scientists to using only 21 approved cell lines out of about 700 in existence. The directive also ordered the NIH to issue new guidelines for hESC research, which were released in July 2009. These new guidelines specify that NIH funding can be provided for research on hESCs derived from human embryos “that were created using in vitro fertilization for reproductive purposes [but] were no longer needed for this purpose,” and were donated by individuals who were fully informed about embryo treatment and gave their voluntary, written consent to use the embryos for research. The guidelines also stipulate that there can be no financial inducements for embryo donations, and that NIH-funded research must remain separate from privately funded research. Additionally, the NIH will establish a working group of scientists and ethicists to review existing cell lines, determine their eligibility for federal funding, and post those hESCs eligible for federal funds in an online registry. The presidential directive greatly expands the research potential in this field, but Obama noted in his remarks about the order that the “full promise of stem cell research remains unknown, and it should not be overstated.” Many advocates of stem cell research agree: Much more stem cell research will take place, yet much more policy work still awaits action. The spotlight is currently on the NIH working group. This is because until the NIH determines which cell lines are eligible for federal funding, hESC research remains on hold and, as of early September 2009, the NIH registry was still empty. Alan Smith, senior research scientist at Stemina Biomarker Discovery (a metabolomics company in Madison, Wisconsin), says that this void in the registry is a major concern for industry because it is slowing efforts to build new collaborations with other companies that are using yet-to-beapproved cell lines and to spur innovations in stem cell research. It is unclear when new stem cell lines will be entered into the registry—no timeline has been announced—but some researchers are concerned that the addition of the new lines may take years. Other pressing policy issues remain. Some analysts have suggested that the government focus on developing a coalition among all the entities that work on stem cells, perhaps by supporting the formation of geographic innovation hubs. Such a large-scale collaboration between universities and industries could be transformative for the field of regenerative medicine. Other experts, such as Jonathan Moreno, a senior fellow at the Center for American Progress, believe that the next grand policy challenge will be to develop guidelines for

Despite the restrictions and controversy confronting stem cell research, labs around the world continue to derive new human embryonic stem cell lines and make them available to the global research community. The EU-funded Human Embryonic Stem Cell Registry (hESCreg) seeks to bring order to the growing number of available stem cell lines and the flood of related data, beginning with the cell lines created in European labs. The web-based registry, launched in January 2008 and accessible at http://www.hescreg.eu, aims to serve as a one-stop source of information about the origins and traits of these cell lines. Anna Veiga, the hESCreg scientific coordinator and director of the stem cell bank at the Centre of Regenerative Medicine in Barcelona, talks with Doug Sipp about how the project was conceived and where it might lead.

Last week, a European team reported creating a line of human embryonic stem cells that did not involve the destruction of human embryos, cultivating a line of stem cells from an "arrested" or nonviable embryo. (Read more.)

FOR THE FIRST TIME, REsearchers have been able to reprogram adult somatic cells to behave like human embryonic stem cells (ESCs) by simply fusing the somatic cells with ESCs from existing stem cell lines ( Science 2005 , 309 , 1369). ESCs are of interest because of their potential to form replacement cells and organs for disease treatment. Until now, published methods to derive ESCs all have involved direct destruction of an embryo. This new process will help scientists understand details about how adult cells can be transformed back to ESCs?information that could provide less ethically charged alternatives to somatic cell nuclear transfer (or therapeutic cloning) for deriving stem cell lines. Word of this new process comes as Congress debates the need to expand the federal ESC research policy which allows federally funded research on a limited number of stem cell lines. The House has already passed legislation to allow federal funds to be used to study additional ESC ...

New treatments based on stem cell technology moved nearer to becoming a realistic possibility, with a UK research group reporting last week that it had successfully cloned a human blastocyst and South Korean researchers reporting that they had created stem cells to match individuals for the first time. Researchers from the University of Newcastle upon Tyne's Centre for Life reported that they had removed the nuclei from oocytes obtained from 11 women and replaced them with DNA from embryonic stem cells. Three of the resulting clones lived and grew in the laboratory for three days, and one survived for five days. The blastocyst had identical DNA to the stem cell line, proving that it had resulted from cloning. The study was published on 19 May in Reproductive and BioMedicine Online (http://www.rbmonline.com/, search for article number 1872). The critical factor for successful cloning seemed to …

The few stem cell lines approved in the United States are probably contaminated with a non-human molecule, says a study published online ahead of print publication in Nature Medicine (www.nature.com/nm/). The researchers recommend starting afresh with human embryonic stem cells that have never been exposed to animal products. The authors, researchers at the University of California at San Diego and the Salk Institute in La Jolla, California, report that the human embryonic stem cells they studied are contaminated with non-human sialic acid that could cause rejection if the stem cells were transplanted into humans. “In …

A LETTER TO CONGRESS FROM NIH Director Elias A. Zerhouni defends the Bush Administration's policy on human embryonic stem cell research while suggesting that more stem cell lines might increase the pace of research. The letter is a response to one from Congress that called for the White House to expand current policy (C&EN, May 3, page 22). Zerhouni, who wrote the letter on behalf of President George W. Bush, outlined NIH's commitment to funding stem cell research that uses the approved 78 cell lines—19 of which are currently usable. He addressed representatives' concerns over the impact of limited federal funding in terms of attracting new scientists and in possibly pushing stem cell research overseas. He also noted that the usable cell lines are sufficient to support basic research. However, he added, it is not clear just what can be accomplished with those cell lines. "And although it is also fair to say ...