National interests and international collaboration: tensions and ambiguity among Finns towards usages of tissue samples

Recent trends in biobanking indicate that the practices associated with the collection and use of human tissue samples and related health information are increasingly becoming premised on networks of biobanks. These networks and partnerships often involve international collaborations, as well as public–private partnerships. This article reports on the results of a study of people's attitudes towards biobanking and the biomedical use of tissue samples in Finland. Three approaches were used to study these attitudes: a population-based survey, focus group interviews among members of patient organizations and short interviews with research participants. In particular, we look at the attitudes of respondents in these three studies towards the use of tissue samples and use them as a catalyst to discuss two dimensions of biomedical research: public/private and domestic/international. Our discussion highlights how notions of value related to the use of tissue samples vary and provide contrasting perspectives and ambiguity that people may have towards various types of research partnerships and the benefits that may arise from them.     

生物样本库及其伦理问题简介

随着分子和基因组信息对流行病学影响的增加,无数遗传流行病学研究和后人类基因组计划的研究都越来越依赖人类生物样本库的使用。生物样本库的范围也已横跨学术或者医院环境下的小数量收集到大规模的全国性储藏。尽管生物样本库的概念并不新,但是在基因组研究和后人类基因组计划的背景下,伴随它们十几年极大发展的是无数待解决的伦理挑战。从生物样本库的概念着手,介绍了其与一般遗传数据库的区别以及建立生物样本库的意义;然后介绍并比较国际上已有的生物样本库,以及其伦理问题和伦理法律框架的发展趋势。     

Biobanks for life sciences and personalized medicine: importance of standardization,biosafety, biosecurity,and data management

Biological samples such as tissues, blood and other body fluids, plants or seeds, prokaryotic and eukaryotic cells or isolated biomolecules as well as associated data are the essential raw material for research and development in medicine, biotechnology and agriculture. The collection, processing, preservation, and storage of these resources, in addition to provision of access, are key activities of biobanks or biological resource centres. Biobanks have to ensure proper quality of samples and data, ethical and legal compliance as well as transparent and efficient access procedures. In this context the review places special emphasis on pre-analytical procedures and international standards, which are essential to improving analytical data reliability and reproducibility, as well as on the increasing importance of data management. These requirements of biobanks are demonstrated using the example of pathogen-containing and microbiome biobanks, and refer to needs in cancer research and development.     

Biobanking and international interoperability: samples

In terms of sample exchange, international collaborations between biobanks, or between biobanks and their research partners, have two important aspects. First, the donors’ consent usually implies that the scope and purpose of any sample transfer to third parties is subject to major constraints. Since the legal, ethical and political framework of biobanking may differ substantially, even between countries of comparable jurisdictional systems, general rules for the international sharing of biomaterial are difficult, if not impossible, to define. Issues of uncertainty include the right to transfer the material, the scope of research allowed, and intellectual property rights. Since suitable means of international law enforcement may not be available in the context of biobanking, collaborators are advised to clarify any residual uncertainty by means of bilateral contracts, for example, in the form of material transfer agreements. Second, biobank partners may rightly expect that the biomaterial they receive for further analysis attains a certain level of quality. This implies that a biobank has to implement stringent quality control measures covering, in addition to the material transfer itself, the whole process of material acquisition, transport, pre-analytical handling and storage. Again, it may be advisable for biobank partners to claim contractual warranties for the type and quality of the biomaterial they wish to acquire.     

Informed consent,and an ethico- legal framework for paediatric observational research and biobanking: the experience of an Italian birth cohort study

Birth cohort studies are important tools for life-course epidemiology, given the spectrum of the environmental, behavioural, and genetic factors that should be considered when making judgements on human health. Biobanks are valuable components of studies designed to investigate the genetic variability of diseases and improve phenotypic characterisation. In studies involving vulnerable populations and biobanks, it is essential to provide ethical reasoning and analyse the legal requirements. We describe the processes and the tools used in the iterative design of an appropriate informed consent model and the ethico-legal framework of the Piccolipiù study. The Piccolipiù study is a prospective population-based study funded by the Italian Ministry of Health that intends to enrol 3,000 newborns and their mothers in five Italian cities, and to store biological samples for future use. To realise these objectives, we performed a thorough evaluation of the literature, of national and international guidelines, and of the impact of the Italian legal requirements for research biobanking. Discussions among stakeholders facilitated the design of the informed consent and the ethico-legal framework. Several topics are addressed, including the suitability of a broad informed consent for paediatric biobanks, infant vulnerability, access to and sharing of data, and the disclosure of individual’s genetic results. Discussion of the ethical and legal procedures adopted in epidemiological biobanking might be a fruitful ground for comparison both at the national level, where standardization and homogeneity are lacking, and at the international level, where different regulatory issues are often in the background and might hamper research biobanks networking.     

Children and biobanks: a review of the ethical and legal discussion

The use of tissue samples from children is vital to genetic research. Collections of such tissue, in so-called biobanks, can take the form of large-scale prospective cohort studies or disease-specific studies using tissue of children with that specific disease. Collections of samples gathered in a diagnostics context, such as blood spot cards, can also be used for genetic research. Research on stored tissue samples from children poses ethical questions that are different from those posed by the use of samples from adults. Also, the ethical questions raised by the participation of children in biobanks are not analogous to those raised by the participation of children in clinical trials. In this review we first give an overview of the international ethical guidelines and legal regulations concerning biobanking and minors. Next, we review the different themes that occur in the ethical literature on this subject. Specifically we focus on questions of risk and benefit, consent and assent and the return of individual results. We also discuss the concept of solidarity, which is a relatively new concept in the context of children and biomedical research. To conclude, we discuss the gaps and questions raised by the review.     

Combining efficiency and concerns about integrity when using human biobanks

In the debate about human bio-sampling the interests of patients and other sample donors are believed to stand against the interests of scientists and of their freedom of research. Scientists want efficient access to and use of human biological samples. Patients and other donors of blood or tissue materials want protection of their integrity. This dichotomy is reflected in the Swedish law on biobanks, which came into effect 1 January 2003. In this article I argue that if the basic interest of scientists using human biological samples is in increasing knowledge and developing better treatments, and if the concept 'integrity' is properly understood, then sample donors should also be interested in promotion of efficiency as well as in the protection of their integrity. The basic premise of this argument is that donors of samples have interests related to the donation and use of samples as well as to the use of the results of the research, that is, new medical products and treatments. They have a role both as donors or participants in research and as end users of the research. I conclude that if (i) access to information acquired through biobank research is strictly limited to researchers, (ii) the information is protected by secrecy safeguards through coding and (iii) the procedures governing the research are open to public and democratic control, then most research using human biobanks may be carried out on the basis of making general information available when collecting biological samples, without further contact with participants.     

Domesticated Animal Biobanking: Land of Opportunity

In the past decade, biobanking has fuelled great scientific advances in the human medical sector. Well-established domesticated animal biobanks and integrated networks likewise harbour immense potential for great scientific advances with broad societal impacts, which are currently not being fully realised. Political and scientific leaders as well as journals and ethics committees should help to ensure that we are well equipped to meet future demands in livestock production, animal models, and veterinary care of companion animals.In the last decade, human biobanking has emerged as an important driver of scientific activities, and biobanks are indisputably an invaluable resource for all types of research aimed at improving public health. The combination of accessible and well-characterized biological samples of various types linked with a multitude of associated data is driving scientific discoveries at unprecedented speed and making previously unthinkable lines of research a reality [1,2].Unfortunately, biobanking of animal samples is by far less well-established. In March 2015, Nature published an article, titled “Inside the first pig biobank,” describing a newly established biobank of porcine samples to be used in studying human diabetes and hailing it as a pioneering effort in animal biobanking [3]. A PubMed search confirmed that in comparison to human biobanking there appears to be negligible activity in the animal biobanking sector. Searching titles, abstracts, and keywords with the search keys “biobank,” “biobanking,” “genebank,” and “gene bank” and limiting the results to publication dates in 2015, only 9 of 498 search results referred to animal biobanks (see S1 Data). This apparent lack of activity in the animal biobanking sector is also reflected in a 2015 editorial of Biopreservation and Biobanking, the official journal of the International Society for Biological and Environmental Repositories (ISBER), which caters to biobanks of any species. The authors conclude that even though there has been increasing participation from the non-human biobanking sector in the annual ISBER meetings, there is still a pronounced lack of submissions to the journal pertaining to non-human biobanking, and human biobanking issues continue to dominate ISBER activities [4]. The roadmap of the European Council’s European Strategy Forum on Research Infrastructures (ESFRI) reveals that there are projects under way involving human (Biobanking and BioMolecular Resources Research Infrastructure [BBMRI]), marine (European Marine Biological Resource Centre [EMBRC]), microbial (Microbial Resource Research Infrastructure [MIRRI]), and mouse model (Infrafrontier) biobanks, with general animal biobanks starkly missing on that list [5].Naturally, some non-human biobanks storing animal samples, amongst others, do exist. The most active are likely the natural history collections, because they have the intrinsic task to collect, catalogue, and store specimens. The Global Genome Biodiversity Network (GGBN), established in 2011, acts as an umbrella organisation for biodiversity repositories and aims to establish standards and best practices as well as increase sample accessibility through its data portal [6]. A search of the most common domesticated animal species (cattle, sheep, goat, pig, horse, chicken, and dog) yielded only 13 records in the GGBN member repositories.However, some domesticated animal biobanks and less formalized sample collections can be found. Their hosting institutions range from veterinary hospitals, zoos, breeding and diagnostics companies, national farm animal genetic resource gene banks, to research institutes and universities. Depending on their purpose, the stored types of samples vary greatly and range from healthy tissue samples, diseased pathogenic tissue samples, DNA, and RNA to reproductive materials. An example of a well-established physical non-human biobanking infrastructure serving a university is the Swedish University of Agricultural Sciences’ (SLU) Biobank (http://www.slu.se/slubiobank). This biobank also offers a data portal for increasing the visibility and accessibility of non-human sample collections no matter where they are stored. This data portal would be redundant if all samples, together with their associated data, were stored in established biobanks that ensured the visibility of their samples through a network such as GGBN. In contrast, the European Genebank Network for Animal Genetic Resources (EUGENA), coordinated by the European Regional Focal Point on Animal Genetic Resources (http://www.rfp-europe.org), is an emerging networking activity specifically targeting only national farm animal genetic resource collections [7]. These disparate examples demonstrate that there is a lack of a unified and generalized approach to sample collections in the domesticated animal sector.Nonetheless, there are numerous examples of how different disciplines and stakeholders, and ultimately the general public, have already benefitted from the availability of biobanked domesticated animal samples.Even though the pig biobank was commended as a pioneering effort [3], there are in fact a number of biobanks that accommodate animal models for the study of human disease. The domestic dog, for example, with its unique population history, breed structure, and hundreds of spontaneous genetic conditions has proven to be an excellent model for gene mapping in simple and complex disorders [8]. Targeted and effective breeding programs over the past 150 years have created hundreds of distinct breeds that form genetic isolates with reduced genetic heterogeneity. This simplifies genetic studies because fewer susceptibility loci with higher impact contribute to complex disease and allow genetic breakthroughs with smaller study cohorts as compared to the corresponding human conditions [9].The annotation of the canine genome facilitated a rapid evolution of genomic tools and development of several canine biobanks across the continents [10]. Collectively, these biobanks house hundreds of thousands of DNA samples and tissue specimens for hundreds of conditions with medical relevance to humans. Importantly, many canine biobanks maintain active collaborative networks with the breeder community and dog fanciers as well as veterinary clinics and hospitals for patient recruitment and health updates.Besides playing an instrumental role for human health, biobanked animal samples heavily impact developments in food production and the sustainable management of the world’s finite resources. Biobanks in animal breeding, often referred to as gene banks, were initially established with the advent of new reproductive techniques, such as artificial insemination, and typically stored semen and embryos. These biobanks recently played a critical role in the swift implementation of genomic selection, which uses genome-wide SNP markers to predict the genetic merit of breeding individuals [11,12]. The efficient use of genomic selection requires large reference panels of individuals whose genetic values are known with high confidence. In cattle breeding, these are bulls with large numbers of offspring with recorded performance data, such as milk yield. Genomic selection could only be implemented so swiftly and successfully because DNA or semen samples from a large number of bulls were available from cattle breeding company biobanks, and these samples could be linked to performance records of the respective bulls’ offspring. This technology was first adopted by the dairy industry and can potentially result in a 60%–120% increase in the rate of genetic gain. Together with advanced genotyping and reproductive technologies, genomic selection has the potential to increase genetic improvement both in often neglected traits, such as feed efficiency and fertility, and in traits that only recently have become of interest, such as methane output in ruminants or adaptation to climate change [12]. Improvements in these traits are of great interest for ensuring global food security and sustainable management of our limited resources. Without the availability of the gene bank samples, as well as associated performance data records, this transformation would have taken decades, if it had happened at all.Biobanks also play an integral part in worldwide conservation efforts to counteract the well-documented loss of genetic diversity in production animals [13,14]. Slowly, the general perception that these repositories are only to be used in emergencies and as a last resort is changing. In 2012, the USDA National Animal Germplasm Program, for example, harboured more than 700,000 gamete and tissue samples from over 18,000 animals representing more than 130 breeds. From this repository, samples from more than 3,300 animals had been requested and distributed for use in research and industry by 2012. The applications included quantitative trait locus (QTL) studies, assessment of genetic distances, cryobiology research, generation of an experimental research line, reduction of inbreeding, and re-introduction of genotypic combinations lost in current production populations [14]. Samples from rare and endangered breeds are also finding use in research and development of the leading breeding companies. For example, in the Netherlands, a consortium of university and dairy industry partners genotyped samples from rare local cattle breeds to gain insight into the genetic background of milk fatty acid composition. Genomic-assisted introgression could ultimately be used to introduce favourable alleles found in the rare breeds into more widely used breeds.Biobanked samples also played an important role in fighting a viral infection, infectious pancreatic necrosis (IPN), which is common in farmed fish. This virus can lead to rates of >90% mortality in farmed Atlantic salmon, which, therefore, poses a threat to animal welfare and aquaculture industries. In 2008, a major QTL for IPN-resistance was detected in Atlantic salmon. Already, a year later, AquaGen, which supplies about 55% of Atlantic salmon eggs used commercially in Norway, was employing marker-assisted selection to produce IPN-resistant fish. This swift implementation of the QTL in marker-assisted selection was only possible due to the availability of biobanked samples collected in a challenge test in 2005 [15].In addition to combatting disease in animals, biobanked domestic animal samples also play a crucial role in fighting emerging infectious diseases that are often zoonotic, meaning that they can be transmitted between vertebrate animals and humans. Having access to samples of species that act as reservoirs of a disease greatly facilitates the work of public health responders during infectious disease outbreaks [16]. In this context, the collection and traceable link of associated samples, such as parasites, pathogens, and other microbiota, to their parent sample becomes especially important.We are convinced that these examples leave no doubt that biobanked animal samples hold great potential both for advancing human and animal health and welfare as well as securing future food production. Furthermore, the recent advent of cost-efficient gene modification technologies [17] envisages many production, performance, and health applications in livestock and companion animals and further adds interest in animal biobanks.When examining the causes for the low levels of activity in large-scale domesticated animal biobanking, both in regard to the establishment or use of existing physical biobanking infrastructures as well as overarching data portals, a number of hypotheses come to mind. The industries connected to domesticated animal biobanking, such as livestock and companion animal production and veterinary care, are dwarfed by the healthcare industry, so monetary incentives would presumably play a much smaller role. Legislation may have acted as a driver in the formalization and shaping of biobanks and differential legislation regarding the handling, storage, and sharing of human versus animal biosamples, and associated data may thus have led to disparate developments. It is moreover conceivable that the community around domesticated animal biobanking is more fragmented and consists of more diverse stakeholders (academic, non-profit, industrial) than the human biobanking community, which could explain the absence of large-scale cooperative umbrella projects. Moreover, there may be greater difficulties in drafting material transfer agreements for reproductive materials than for other types of samples.We will only be able to exploit the full potential if we, in parallel with human and biodiversity biobanking, tackle the challenges of standardized sampling, processing, and storage, sample visibility and accessibility, standardized codes for diagnoses, collection and storage of associated data with the possibility for updates, as well as ethical and regulatory issues. Here, it is advisable that the domesticated animal sector ensures full compatibility with and relies on existing initiatives wherever feasible. Especially important in this context is to ensure a link between samples and associated phenomic and genomic data, such as derived sequence data. To achieve agreement on standards, both in terms of sample processing and storage and sample visibility and accessibility, actors from veterinary hospitals, zoos, breeding and diagnostics companies, national farm animal genetic resource gene banks, research institutes, universities, and policymakers need to join forces. This is where we momentarily see a lack of coordinated efforts.To respond to these challenges and to ensure that we are well equipped to meet future demands in livestock production, animal models, and veterinary care of companion animals, we propose that scientific and political leaders need to (i) acknowledge the inadequacy of the current situation, (ii) create opportunity and support for the establishment of an international research infrastructure for animal biobanking, and (iii) motivate academic and industrial stakeholders to develop and coordinate biobanks based on lessons learned from human and biodiversity biobanking.In Europe, the European Council’s ESFRI could play a leading role in the establishment of a domesticated animal biobanking network, including best practices, direly needed standards, and a common ontology. In a landscape analysis of European research infrastructures, the 2016 ESFRI roadmap acknowledges a gap in the agricultural and bio-economy sector and explicitly lists livestock facilities including gene banks [5]. While an increase in activities regarding biobanking of farm animal genetic resources is certainly relevant, we consider this not to be far-reaching enough. A step in the right direction would be to begin with compiling information on all existing animal biobanks, analogous to BBMRI’s catalogue for European human biobanks [18], which currently contains information on 340 biobanks (http://www.bbmriportal.eu/).Moreover, ethics committees should require the storage of samples and associated data in formalized biobanks for the approval of scientific experiments. Similarly, journals should apply the same standard to samples and associated data, as they currently apply to molecular data, in terms of storage in formalized repositories prior to publication.     

Biobanken

Biobanks have become an indispensable component of biomedical research. However, the long-term and unrestricted use of data and biomaterials included in most biobanks pose several legal, ethical and organizational challenges. Therefore, the German Telematics Platform for Medical Research Networks (TMF) has instigated a number of projects addressing the problems arising from the establishment and maintenance of biobanks, each time aiming at the provision of generic solutions to the research community in the form of texts and concepts. After a representative review of existing biobanks in Germany and Europe we provide an overview of the TMF work on biobanking. In addition, two infrastructural projects will be reviewed which should render biobanking in Germany and Europe more efficient and transparent in the future, namely the “Biobanking and Biomolecular Resources Research Infrastructure”(BBMRI) of the European Commission and the National Biobank Register that is currently being set up by the TMF.     

Biobanks for genomics and genomics for biobanks

Biobanks include biological samples and attached databases. Human biobanks occur in research, technological development and medical activities. Population genomics is highly dependent on the availability of large biobanks. Ethical issues must be considered: protecting the rights of those people whose samples or data are in biobanks (information, autonomy, confidentiality, protection of private life), assuring the non-commercial use of human body elements and the optimal use of samples and data. They balance other issues, such as protecting the rights of researchers and companies, allowing long-term use of biobanks while detailed information on future uses is not available. At the level of populations, the traditional form of informed consent is challenged. Other dimensions relate to the rights of a group as such, in addition to individual rights. Conditions of return of results and/or benefit to a population need to be defined. With 'large-scale biobanking' a marked trend in genomics, new societal dimensions appear, regarding communication, debate, regulation, societal control and valorization of such large biobanks. Exploring how genomics can help health sector biobanks to become more rationally constituted and exploited is an interesting perspective. For example, evaluating how genomic approaches can help in optimizing haematopoietic stem cell donor registries using new markers and high-throughput techniques to increase immunogenetic variability in such registries is a challenge currently being addressed. Ethical issues in such contexts are important, as not only individual decisions or projects are concerned, but also national policies in the international arena and organization of democratic debate about science, medicine and society.     

Reflexive governance in biobanking: on the value of policy led approaches and the need to recognise the limits of law

Although a few jurisdictions around the world have legislated in response to the phenomenon of biobanking, the far more common response has been policy led with funders and other stakeholders initiating multi-level policy initiatives to guide biobanking practice. An example of this is UK Biobank which has developed and operates according to an Ethics and Governance Framework. Such an instrument has no basis in law and yet it has played a crucial role in the set up and ongoing management of the resource. It will continue to do so, as related policies emerge, such as access and intellectual property policies. Numerous biobanking initiatives have similar high-level policy documents that guide decisions and practice. These are often framed as a commitment to participants, researchers and society more broadly and invoke notions such as the public good and the public interest. As such, they serve as a benchmark against which to measure a biobank’s performance. Moreover, policies become an important means by which biobankers are held accountable. This article critically analyses this policy-driven phenomenon asking how effectively policy—often as an alternative to law—serves to police and to promote biobanking. It argues that a policy of reflexive governance—defined and developed herein—can best meet the challenges faced by many biobanks and without the need for recourse to law.     

Closure of population biobanks and direct-to-consumer genetic testing companies

Genetic research gained new momentum with the completion of the Human Genome Project in 2003. Formerly centered on the investigation of single-gene disorders, genetic research is increasingly targeting common complex diseases and in doing so is studying the whole genome, the environment and its impact on genomic variation. Consequently, biobanking initiatives have emerged around the world as a tool to sustain such progress. Whether they are small scale or longitudinal, public or private, commercial or non-commercial, biobanks should consider the possibility of closure. Interestingly, while raising important ethical issues, this topic has hardly been explored in the literature. Indeed, ethical issues associated with sale, insolvency, end of funding, or transfer of materials to other entities (which are all issues either related to or possible consequences of closure) are seldom the subject of discussion. In an attempt to fill this gap, this paper will discuss—using population and direct-to-consumer (DTC) genetic testing companies’ biobanks as case studies—(1) international and national normative documents addressing the issue of closure and (2) the internal policies of population biobanks and DTC genetic testing companies. The analysis will inform the debate on biobank closure and elucidate the underlying ethical issues, which include, but are not limited to informed consent, storage and privacy.     

“Good Mothering” or “Good Citizenship”? Conflicting Values in Choosing Whether to Donate or Store Umbilical Cord Blood

Umbilical cord blood banking is one of many biomedical innovations that confront pregnant women with new choices about what they should do to secure their own and their child’s best interests. Many mothers can now choose to donate their baby’s umbilical cord blood (UCB) to a public cord blood bank or pay to store it in a private cord blood bank. Donation to a public bank is widely regarded as an altruistic act of civic responsibility. Paying to store UCB may be regarded as a “unique opportunity” to provide “insurance” for the child’s future. This paper reports findings from a survey of Australian women that investigated the decision to either donate or store UCB. We conclude that mothers are faced with competing discourses that force them to choose between being a “good mother” and fulfilling their role as a “good citizen.” We discuss this finding with reference to the concept of value pluralism.     

Beyond and within public engagement: a broadened approach to engagement in biobanking

Social studies on biobanking have traditionally focused on public engagement, that is, engagement with donors, patients and the general public as an important factor of sustainability. In this article, we claim that, in order to fully understand the way biobanks work, it is necessary to pay attention to a number of other actors, which have an equal, if not greater, impact on their practices and strategies. This means taking a broadened approach to biobank engagement. By using data collected from interviews with different biobank experts based in five different countries (UK, Canada, Finland, Spain and Iceland), we identify seven communities, including the public, that emerge as relevant. Such relationships condition the way biobanks develop, act and plan. The discussion illustrates how the relationships with those seven communities are articulated. We conclude that there is a need for a broadened approach to biobank engagement in order to understand biobank sustainability.     

Yin-yang genetics,or the HSD deCODE controversy

This paper examines a number of social, ethical and cultural issues related to the application of biotechnology. The focus of the paper relies on two different cases of governing biotechnology in Portugal, referring to donation of biological material: the act of donation of eggs and sperm; and volunteers for donation of DNA material for the forensic national DNA database. We analyze the discourses on donation of biological material framing them in rhetorical devices of gift, altruism, informed consent and social responsibility. This comes blended with still unclear and emergent regulation and policies of access, retention, preservation and governing of biological material and of donors' identification. The risks are mitigated by narratives of science and technology as social progress and providers of public good and health benefits, as well as by underlining the individual responsibility in this domain and by reinforcing the rhetoric of gene quality, based on socio-cultural and bio-genetic criteria.     

Allogenic banking of dental pulp stem cells for innovative therapeutics

Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.     

Spontaneous and stimulated interleukin-6 and tumor necrosis factor-alpha production at delivery and three months after birth

OBJECTIVE: To study the production and interrelations of maternal and neonatal cytokines (IL-6 and TNF-alpha) during labor, after vaginal delivery and at three months after delivery. METHOD: The unstimulated concentrations of cytokines in the supernatants of whole-blood cultures and concentrations after PMA (phorbol 12-myristate 13-acetate) and concanavalin (conA) stimulation were determined by enzyme-linked immunosorbent assays (ELISAs). The blood samples were from the peripheral veins of 27 healthy women during term labor and immediately after delivery and three months after delivery. Neonatal samples were taken at birth (cord blood) and three months after delivery. RESULTS: IL-6 responses to stimulation were increased in the parturients and in umbilical cord blood at delivery compared with maternal and neonatal samples obtained 3 months postpartum. In contrast, the production of maternal TNF-alpha in peripheral blood was down-regulated at delivery compared with values 3 months postpartum. After an IL-6 and TNF-alpha burst in umbilical cord samples, neonatal cytokine production was at a low level three months after delivery. IL-6 production tended to be higher in both umbilical cord blood as well as in maternal samples after delivery in women who were younger. In addition, TNF-alpha production in umbilical cord blood was significantly higher in those women who were younger. CONCLUSIONS: The production of IL-6 was up-regulated in both the maternal and in umbilical cord blood at delivery. The production of TNF-alpha was up-regulated in umbilical cord blood compared with neonatal values 3 months after birth. Maternal age had effects on IL-6 and TNF-alpha production at delivery.     

Standard operating procedures for pre-analytical handling of blood and urine for metabolomic studies and biobanks

(1)H NMR metabolic profiling of urine, serum and plasma has been used to monitor the impact of the pre-analytical steps on the sample quality and stability in order to propose standard operating procedures (SOPs) for deposition in biobanks. We analyzed the quality of serum and plasma samples as a function of the elapsed time (t?=?0-4?h) between blood collection and processing and of the time from processing to freezing (up to 24?h). The stability of the urine metabolic profile over time (up to 24?h) at various storage temperatures was monitored as a function of the different pre-analytical treatments like pre-storage centrifugation, filtration, and addition of the bacteriostatic preservative sodium azide. Appreciable changes in the profiles, reflecting changes in the concentration of a number of metabolites, were detected and discussed in terms of chemical and enzymatic reactions for both blood and urine samples. Appropriate procedures for blood derivatives collection and urine preservation/storage that allow maintaining as much as possible the original metabolic profile of the fresh samples emerge, and are proposed as SOPs for biobanking.     

Quality matters: International standards for biobanking

Human biospecimens provide the basis for research, leading to a better understanding of human disease biology and discovery of new treatments that are tailored to individual patients with cancer or other common complex diseases. The collection, processing, preservation, storage and providing access to these resources are key activities of biobanks. Biobanks must ensure proper quality of samples and data, ethical and legal compliance as well as transparent and efficient access procedures. The standards for biobanking outlined herein are intended to be implemented in biobanks and to supply researchers with high‐quality samples fitted for an intended use.

Several variables in the pre‐analytical phase can affect the quality of biological samples. © K. Zatloukal.     

Towards responsible cord blood banking models

On 31 May 2010, 14 072 567 bone marrow/apheresis donors registered in 44 countries and 426 501 cord blood units banked in 26 countries for public use were available to treat candidates to haemopoietic stem cell transplant lacking a family related compatible donor. Despite these impressive numbers, additional efforts are required to ensure that all patients, including those from ethnic minorities, can promptly find a suitable donor. Governments, clinicians, scientists, patients and stakeholders should share the responsibility to develop haemopoietic stem cell donation and cord blood banking models able to fully match all patient needs. In this regard, current scientific evidence and prevalent opinions among expert clinicians support solidaristic cord blood donation for public use against the alternative option of commercial autologous cord blood storage.