Locating tissue collections in tissue economies—deriving value from biomedical research

Abstract

This paper examines diverging notions of value in the use of tissue sample collections and other information resources using a case study of hereditary colorectal cancer research in Finland. Recent science and technology policies that emphasize the production of commercial value derived from tissue sample collections are challenged by varying conceptions of value, as well as structural factors that relate to the combination of different public population information systems in the Finnish research system. Such challenges reflect a tension in the economic aspirations of the ideology of the knowledge society in relation to the goals of national health care policies, as well as the role of the state as a mediator of knowledge production and commercial development.     

Chondrogenesis and cartilage tissue engineering: the longer road to technology development

Joint injury and disease are painful and debilitating conditions affecting a substantial proportion of the population. The idea that damaged cartilage in articulating joints might be replaced seamlessly with tissue-engineered cartilage is of obvious commercial interest because the market for such treatments is large. Recently, a wealth of new information about the complex biology of chondrogenesis and cartilage has emerged from stem cell research, including increasing evidence of the role of physical stimuli in directing differentiation. The challenge for the next generation of tissue engineers is to identify the key elements in this new body of knowledge that can be applied to overcome current limitations affecting cartilage synthesis in vitro. Here we review the status of cartilage tissue engineering and examine the contribution of stem cell research to technology development for cartilage production.     

Impact of genomics on animal agriculture and opportunities for animal health

Livestock production is an important source of animal protein worldwide. In the developed world meat consumption will remain steady but demand is forecast to grow enormously in developing countries. The use of genomics will speed genetic improvement and increase levels of production quickly in the developed world but might face problems in the developing world, including scientific, economic and political challenges. Considerable increases in public and private research funding will be required to develop and utilize novel tools and collections of detailed trait information on appropriate animals. The development of policies protecting the environment and managing all genetic resources will also be needed. Advances in livestock genomics have major implications for increasing food output as well as improving human health.     

The use of stored tissue samples from minors for genetic research: interviews with professionals

Stored tissue sample collections from minors are useful for genetic research. The ethics of the use of stored tissue samples for genetic research continues be a much debated topic of discussion. The use of pediatric samples poses specific ethical questions. Although a substantial corpus of empirical literature exists on the use of samples from adults, not much is known about the opinion of professionals on the use of samples from children. We conducted ten interviews with professionals in the field. Their primary concerns were the fact that consent procedures should not be too bureaucratic, the need for proper research design and privacy protections, the fact that research should not burden children and guidance from ethics committees.     

Proteome analysis of microdissected formalin-fixed and paraffin-embedded tissue specimens.

Targeted proteomics research, based on the enrichment of disease-relevant proteins from isolated cell populations selected from high-quality tissue specimens, offers great potential for the identification of diagnostic, prognostic, and predictive biological markers for use in the clinical setting and during preclinical testing and clinical trials, as well as for the discovery and validation of new protein drug targets. Formalin-fixed and paraffin-embedded (FFPE) tissue collections, with attached clinical and outcome information, are invaluable resources for conducting retrospective protein biomarker investigations and performing translational studies of cancer and other diseases. Combined capillary isoelectric focusing/nano-reversed-phase liquid chromatography separations equipped with nano-electrospray ionization-tandem mass spectrometry are employed for the studies of proteins extracted from microdissected FFPE glioblastoma tissues using a heat-induced antigen retrieval (AR) technique. A total of 14,478 distinct peptides are identified, leading to the identification of 2733 non-redundant SwissProt protein entries. Eighty-three percent of identified FFPE tissue proteins overlap with those obtained from the pellet fraction of fresh-frozen tissue of the same patient. This large degree of protein overlapping is attributed to the application of detergent-based protein extraction in both the cell pellet preparation protocol and the AR technique.     

Evaporation process in histological tissue sections for neutron autoradiography

The analysis of the distribution and density of nuclear tracks forming an autoradiography in a nuclear track detector (NTD) allows the determination of ¹⁰B atoms concentration and location in tissue samples from Boron Neutron Capture Therapy (BNCT) protocols. This knowledge is of great importance for BNCT dosimetry and treatment planning. Tissue sections studied with this technique are obtained by cryosectioning frozen tissue specimens. After the slicing procedure, the tissue section is put on the NTD and the sample starts drying. The thickness varies from its original value allowing more particles to reach the detector and, as the mass of the sample decreases, the boron concentration in the sample increases. So in order to determine the concentration present in the hydrated tissue, the application of corrective coefficients is required. Evaporation mechanisms as well as various factors that could affect the process of mass variation are outlined in this work. Mass evolution for tissue samples coming from BDIX rats was registered with a semimicro analytical scale and measurements were analyzed with software developed to that end. Ambient conditions were simultaneously recorded, obtaining reproducible evaporation curves. Mathematical models found in the literature were applied for the first time to this type of samples and the best fit of the experimental data was determined. The correlation coefficients and the variability of the parameters were evaluated, pointing to Page’s model as the one that best represented the evaporation curves. These studies will contribute to a more precise assessment of boron concentration in tissue samples by the Neutron Autoradiography technique.     

Proteomic analysis of formalin-fixed paraffin-embedded tissue by MALDI imaging mass spectrometry

Archived formalin-fixed paraffin-embedded (FFPE) tissue collections represent a valuable informational resource for proteomic studies. Multiple FFPE core biopsies can be assembled in a single block to form tissue microarrays (TMAs). We describe a protocol for analyzing protein in FFPE-TMAs using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). The workflow incorporates an antigen retrieval step following deparaffinization, in situ trypsin digestion, matrix application and then mass spectrometry signal acquisition. The direct analysis of FFPE-TMA tissue using IMS allows direct analysis of multiple tissue samples in a single experiment without extraction and purification of proteins. The advantages of high speed and throughput, easy sample handling and excellent reproducibility make this technology a favorable approach for the proteomic analysis of clinical research cohorts with large sample numbers. For example, TMA analysis of 300 FFPE cores would typically require 6 h of total time through data acquisition, not including data analysis.     

Efficacy of long-term coral tissue storage in ethanol for genotyping studies

With climate change threatening the future of coral reefs, there is an urgent need for effective coral tissue preservation and repositories from which DNA can be extracted. Most collections use 95 % ethanol as the storage medium, but its efficacy for long-term storage for short-fragment DNA use remains poorly documented. We conducted an accelerated DNA aging trial on three species of coral to ascertain whether ethanol-stored tissue and skeleton samples could yield fit-for-purpose DNA at time scales of 100+ yrs. We conclude that even using a crude DNA extraction technique, samples kept at 40 °C for 20 months yielded DNA of sufficient quality for Symbiodinium and coral host genotyping. If stored at ?20 °C, these samples are likely to still yield useable DNA after 100 yrs. Ethanol-stored samples compared favorably in terms of DNA quality, quantity and sample integrity with those stored in an analogue of the commercial storage buffer RNAlater ^®.     

Supply and use of human tissue for research purposes: survey of BATB affiliated tissue banks

This paper describes a survey undertaken to identify the extent of supply and use of human tissue in research by BATB affiliated tissue banks. Approximately one third of tissue banks registered with the BATB are currently supplying samples that are found to be unsuitable for clinical use, for research. These banks all obtain consent for research and all supply tissue for in-house research. Some tissue is transferred to other public and commercial institutions. A harmonised network approach is proposed as the way forward to meet the increasing demand for human tissue in research.     

Recent progress in the understanding of tissue culture-induced genome level changes in plants and potential applications

In vitro cell and tissue-based systems have tremendous potential in fundamental research and for commercial applications such as clonal propagation, genetic engineering and production of valuable metabolites. Since the invention of plant cell and tissue culture techniques more than half a century ago, scientists have been trying to understand the morphological, physiological, biochemical and molecular changes associated with tissue culture responses. Establishment of de novo developmental cell fate in vitro is governed by factors such as genetic make-up, stress and plant growth regulators. In vitro culture is believed to destabilize the genetic and epigenetic program of intact plant tissue and can lead to chromosomal and DNA sequence variations, methylation changes, transposon activation, and generation of somaclonal variants. In this review, we discuss the current status of understanding the genomic and epigenomic changes that take place under in vitro conditions. It is hoped that a precise and comprehensive knowledge of the molecular basis of these variations and acquisition of developmental cell fate would help to devise strategies to improve the totipotency and embryogenic capability in recalcitrant species and genotypes, and to address bottlenecks associated with clonal propagation.     

Knowledge sharing and collaboration in translational research, and the DC-THERA Directory

Biomedical research relies increasingly on large collections of data sets and knowledge whose generation, representation and analysis often require large collaborative and interdisciplinary efforts. This dimension of 'big data' research calls for the development of computational tools to manage such a vast amount of data, as well as tools that can improve communication and access to information from collaborating researchers and from the wider community. Whenever research projects have a defined temporal scope, an additional issue of data management arises, namely how the knowledge generated within the project can be made available beyond its boundaries and life-time. DC-THERA is a European 'Network of Excellence' (NoE) that spawned a very large collaborative and interdisciplinary research community, focusing on the development of novel immunotherapies derived from fundamental research in dendritic cell immunobiology. In this article we introduce the DC-THERA Directory, which is an information system designed to support knowledge management for this research community and beyond. We present how the use of metadata and Semantic Web technologies can effectively help to organize the knowledge generated by modern collaborative research, how these technologies can enable effective data management solutions during and beyond the project lifecycle, and how resources such as the DC-THERA Directory fit into the larger context of e-science.     

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.     

Mass digitization of scientific collections: New opportunities to transform the use of biological specimens and underwrite biodiversity science

New information technologies have enabled the scientific collections community and its stakeholders to adapt, adopt, and leverage novel approaches for a nearly 300 years old scientific discipline. Now, few can credibly question the transformational impact of technology on efforts to digitize scientific collections, as IT now reaches into almost every nook and cranny of society. Five to ten years ago this was not the case. Digitization is an activity that museums and academic institutions increasingly recognize, though many still do not embrace, as a means to boost the impact of collections to research and society through improved access. The acquisition and use of scientific collections is a global endeavor, and digitization enhances their value by improved access to core biodiversity information, increases use, relevance and potential downstream value, for example, in the management of natural resources, policy development, food security, and planetary and human health. This paper examines new opportunities to design and implement infrastructure that will support not just mass digitization efforts, but also a broad range of research on biological diversity and physical sciences in order to make scientific collections increasingly relevant to societal needs and interest.     

Biological collections and ecological/environmental research: a review,some observations and a look to the future

Housed worldwide, mostly in museums and herbaria, is a vast collection of biological specimens developed over centuries. These biological collections, and associated taxonomic and systematic research, have received considerable long‐term public support. The work remaining in systematics has been expanding as the estimated total number of species of organisms on Earth has risen over recent decades, as have estimated numbers of undescribed species. Despite this increasing task, support for taxonomic and systematic research, and biological collections upon which such research is based, has declined over the last 30‐40 years, while other areas of biological research have grown considerably, especially those that focus on environmental issues. Reflecting increases in research that deals with ecological questions (e.g. what determines species distribution and abundance) or environmental issues (e.g. toxic pollution), the level of research attempting to use biological collections in museums or herbaria in an ecological/environmental context has risen dramatically during about the last 20 years. The perceived relevance of biological collections, and hence the support they receive, should be enhanced if this trend continues and they are used prominently regarding such environmental issues as anthropogenic loss of biodiversity and associated ecosystem function, global climate change, and decay of the epidemiological environment. It is unclear, however, how best to use biological collections in the context of such ecological/environmental issues or how best to manage collections to facilitate such use. We demonstrate considerable and increasingly realized potential for research based on biological collections to contribute to ecological/environmental understanding. However, because biological collections were not originally intended for use regarding such issues and have inherent biases and limitations, they are proving more useful in some contexts than in others. Biological collections have, for example, been particularly useful as sources of information regarding variation in attributes of individuals (e.g. morphology, chemical composition) in relation to environmental variables, and provided important information in relation to species' distributions, but less useful in the contexts of habitat associations and population sizes. Changes to policies, strategies and procedures associated with biological collections could mitigate these biases and limitations, and hence make such collections more useful in the context of ecological/environmental issues. Haphazard and opportunistic collecting could be replaced with strategies for adding to existing collections that prioritize projects that use biological collections and include, besides taxonomy and systematics, a focus on significant environmental/ecological issues. Other potential changes include increased recording of the nature and extent of collecting effort and information associated with each specimen such as nearby habitat and other individuals observed but not collected. Such changes have begun to occur within some institutions. Institutions that house biological collections should, we think, pursue a mission of ‘understanding the life of the planet to inform its stewardship’ ( Krishtalka & Humphrey, 2000 ), as such a mission would facilitate increased use of biological collections in an ecological/environmental context and hence lead to increased appreciation, encouragement and support from the public for these collections, their associated research, and the institutions that house them.     

Plant tissue culture environment as a switch-key of (epi)genetic changes

Plant Cell, Tissue and Organ Culture (PCTOC) - The in vitro tissue cultures are, beyond all difficulties, an essential tool in basic research as well as in commercial applications. Numerous works...     

Phycobiliproteins as a commodity: trends in applied research,patents and commercialization

Phycobiliproteins are a group of colored proteins commonly present in cyanobacteria and red algae possessing a spectrum of applications. They are extensively commercialized for fluorescent applications in clinical and immunological analysis. They are also used as a colorant, and their therapeutic value has also been categorically demonstrated. However, a comprehensive knowledge and technological base for augmenting their commercial utilities is lacking. Hence, this work is focused towards this objective by means of analyzing global patents and commercial activities with application oriented research. Strategic mining of patents was performed from global patent databases resulting in the identification of 297 patents on phycobiliproteins. The majority of the patents are from USA, Japan and Europe. Patents are grouped into fluorescent applications, general applications and production aspects of phycobiliproteins and the features of each group are discussed. Commercial and applied research activities are compared in parallel. It revealed that US patents are mostly related to fluorescent applications while Japanese are on the production, purification and application for therapeutic and diagnostic purposes. Fluorescent applications are well represented in research, patents and commercial sectors. Biomedical properties documented in research and patents are not ventured commercially. Several novel applications are reported only in patents. The paper further pinpoints the plethora of techniques used for cell breakage and for extraction and purification of phycobiliproteins. The analysis identifies the lacuna and suggests means for improvements in the application and production of phycobiliproteins.     

Quality control of human tissues-experience from the Indiana University Cancer Center-Lilly Research Labs human tissue bank

The success of molecular research and its applications in both the clinical and basic research arenas is strongly dependent on the collection, handling, storage, and quality control of fresh human tissue samples. This tissue bank was set up to bank fresh surgically obtained human tissue using a Clinical Annotated Tissue Database (CATD) in order to capture the associated patient clinical data and demographics using a one way patient encryption scheme to protect patient identification. In this study, we determined that high quality of tissue samples is imperative for both genomic and proteomic molecular research. This paper also contains a brief compilation of the literature involved in the patient ethics, patient informed consent, patient de-identification, tissue collection, processing, and storage as well as basic molecular research generated from the tissue bank using good clinical practices. The current applicable rules, regulations, and guidelines for handling human tissues are briefly discussed. More than 6,610 cancer patients have been consented (97% of those that were contacted by the consenter) and 16,800 tissue specimens have been banked from these patients in 9 years. All samples collected in the bank were QC’d by a pathologist. Approximately 1,550 tissue samples have been requested for use in basic, clinical, and/or biomarker cancer research studies. Each tissue aliquot removed from the bank for a research study were evaluated by a second H&E, if the samples passed the QC, they were submitted for genomic and proteomic molecular analysis/study. Approximately 75% of samples evaluated were of high histologic quality and used for research studies. Since 2003, we changed the patient informed consent to allow the tissue bank to gather more patient clinical follow-up information. Ninety two percent of the patients (1,865 patients) signed the new informed consent form and agreed to be re-contacted for follow-up information on their disease state. In addition, eighty five percent of patients (1,584) agreed to be re-contacted to provide a biological fluid sample to be used for biomarker research.     

Collecting collections: building the library of The New York Botanical Garden

The history of the collections in the Library of The New York Botanical Garden includes the acquisition of previously accumulated collections as well as individual items acquired in the normal course of collection development. Particularly during the first 50 years of the institution, collections of library materials were acquired along with herbaria specimens, and, occasionally, collections of living plants, assembled by an individual as part of his or her personal research interests. While curatorial practice dictates that such an assemblage of research materials be separated when shifted from individual to institutional curatorship, the knowledge of the whole of the collection as received may fill in the background pattern of institutional collection development. A chronological table of these collections is appended, including reference to any extended discussion or listing.