NCI SEER-Linked Virtual Tissue Repository Pilot.

BACKGROUND: The Surveillance, Epidemiology, and End Results (SEER) Program with the National Cancer Institute tested whether population-based cancer registries can serve as honest brokers to acquire tissue and data in the SEER-Linked Virtual Tissue Repository (VTR) Pilot. METHODS: We collected formalin-fixed, paraffin-embedded tissue and clinical data from patients with pancreatic ductal adenocarcinoma (PDAC) and breast cancer (BC) for two studies comparing cancer cases with highly unusual survival (≥5 years for PDAC and ≤30 months for BC) to pair-matched controls with usual survival (≤2 years for PDAC and ≥5 years for BC). Success was defined as the ability for registries to acquire tissue and data on cancer cases with highly unusual outcomes. RESULTS: Of 98 PDAC and 103 BC matched cases eligible for tissue collection, sources of attrition for tissue collection were tissue being unavailable, control paired with failed case, second control that was not requested, tumor necrosis ≥20%, and low tumor cellularity. In total, tissue meeting the study criteria was obtained for 70 (71%) PDAC and 74 (72%) BC matched cases. For patients with tissue received, clinical data completeness ranged from 59% for CA-19-9 after treatment to >95% for margin status, whether radiation therapy and chemotherapy were administered, and comorbidities. CONCLUSIONS: The VTR Pilot demonstrated the feasibility of using SEER cancer registries as honest brokers to provide tissue and clinical data for secondary use in research. Studies using this program should oversample by 45% to 50% to obtain sufficient sample size and targeted population representation and involve subspecialty matter expert pathologists for tissue selection.

Smoking exposure and Parkinson's disease: A UK Brain Bank pathology-validated case-control study.

INTRODUCTION: Epidemiological studies have consistently shown an inverse association between cigarette smoking and Parkinson's disease. Literature indicates that both current and former smokers have a reduced risk of developing PD compared to non-smokers. If smoking protects against Parkinson's disease risk or, conversely, smoking habit is abated due to the disease itself, according to the reverse causation, is still an unsolved question. METHODS: 118 patients from the UK Brain Bank with an alive clinical diagnosis of Parkinson's disease were enrolled. Post-mortem validation served as the gold standard for diagnosis to divide the population into true positive and false positive groups. Patient charts were reviewed to extract smoking exposure information and statistical analyses were conducted to determine the odds associated with smoking in the two diagnostic groups. RESULTS: Among alive clinically diagnosed patients with Parkinson's disease, 53 % had no smoking exposure. In the True Positive group, 58 % had no smoking exposure, while this proportion was lower in the False Positive group at 46 %. The Odds Ratio for the association between smoking exposure and the two groups was 0.63 (95 % CI: 0.32-1.37). The Chi-square test yielded a p-value of 0.2804. CONCLUSIONS: Our findings emphasize the role of smoking exposure in Parkinson's diagnosis. The results indicate that the observed association is not specific to idiopathic Parkinson's disease but rather a broader phenomenon encompassing various parkinsonian disorders. This suggests a potential common neuroprotective effect of smoking, shared risk factors, or supports the reverse causation hypothesis where parkinsonian symptoms reduce smoking exposure.

[National and world experience in functioning of centers for collective use of biological resource collections of tumors of the central nervous system]. / Analiz mirovogo i otechestvennogo opyta funktsionirovaniya tsentrov kollektivnogo pol'zovaniya bioresursnymi kollektsiyami opukholei tsentral'noi nervnoi sistemy.

Collective use center is an organization or structural unit with unique resource providing access to this resource for internal and third-party users. Collective use centers are a relatively new phenomenon in bioresource collections, especially collections of human biological material due to some ethical and legal issues. At the same time, the demand for human biological material continues to grow in fundamental and applied researches. The collective use center «Bioresource collection of tissues and cell cultures of tumors of the human nervous system for fundamental and applied researches¼ has worked since October 14, 2022. This center has access to unique collection of the Laboratory of Neurosurgical Anatomy and Conservation of Human Biological Tissues of the Burdenko Neurosurgical Center. OBJECTIVE: To analyze the experience of collective use center and biobank of the Burdenko Neurosurgical Center compared to national and international data on functioning of collective use centers specializing in tumors of the human central nervous system. MATERIAL AND METHODS: We reviewed the PubMed and e-Library databases using the following keywords: core facilities brain tumors, repository of collective use brain tumors, biobank of CNS tumors, central nervous system tumor collection centers. We also analyzed the organizations registered on the portal of scientific and technical infrastructure of the Russian Federation. RESULTS: We analyzed 275 publications devoted to collective use centers and biobanks. These biobanks do not position themselves as collective use centers but actively realize biological material for researches. Structure of institutions presented on the portal of scientific and technical infrastructure of the Russian Federation is characterized. The collective use center «Bioresource collection of tissues and cell cultures of tumors of the human nervous system for fundamental and applied researches¼ has access to biobank of the Burdenko Neurosurgical Center. To date, the biobank contains more than 8478 aliquots of tumor tissue frozen at ultra-low temperature (-196°C) and obtained from 1993 patients. Considering available data, we established the basic principles of work in collective use centers with bioresource collections. CONCLUSION: Collective use centers with bioresource collections of tumors of the central nervous system are rare. There is only one collective use center organized at the Burdenko Neurosurgical Center on the portal of scientific and technical infrastructure of the Russian Federation. At the same time, there is an urgent need to increase their number and activity in Russia and other countries worldwide. You can use the resource of brain tumor collections by leaving a request on the official website of this organization in the «Collective use center¼ section.

Impact of the delay in cryopreservation timing during biobanking procedures on human liver tissue metabolomics.

The liver is a highly specialized organ involved in regulating systemic metabolism. Understanding metabolic reprogramming of liver disease is key in discovering clinical biomarkers, which relies on robust tissue biobanks. However, sample collection and storage procedures pose a threat to obtaining reliable results, as metabolic alterations may occur during sample handling. This study aimed to elucidate the impact of pre-analytical delay during liver resection surgery on liver tissue metabolomics. Patients were enrolled for liver resection during which normal tissue was collected and snap-frozen at three timepoints: before transection, after transection, and after analysis in Pathology. Metabolomics analyses were performed using 1H Nuclear Magnetic Resonance (NMR) and Liquid Chromatography-Mass Spectrometry (LC-MS). Time at cryopreservation was the principal variable contributing to differences between liver specimen metabolomes, which superseded even interindividual variability. NMR revealed global changes in the abundance of an array of metabolites, namely a decrease in most metabolites and an increase in ß-glucose and lactate. LC-MS revealed that succinate, alanine, glutamine, arginine, leucine, glycerol-3-phosphate, lactate, AMP, glutathione, and NADP were enhanced during cryopreservation delay (all p<0.05), whereas aspartate, iso(citrate), ADP, and ATP, decreased (all p<0.05). Cryopreservation delays occurring during liver tissue biobanking significantly alter an array of metabolites. Indeed, such alterations compromise the integrity of metabolomic data from liver specimens, underlining the importance of standardized protocols for tissue biobanking in hepatology.

Disentangling the heterogeneity of multiple sclerosis through identification of independent neuropathological dimensions.

Multiple sclerosis (MS) is a heterogeneous neurological disorder with regards to clinical presentation and pathophysiology. Here, we investigated the heterogeneity of MS by performing an exploratory factor analysis on quantitative and qualitative neuropathology data collected for 226 MS donors in the Netherlands Brain Bank autopsy cohort. Three promising dimensions were identified and subsequently validated with clinical, neuropathological, and genetic data. Dimension 1 ranged from a predominance of remyelinated and inactive lesions to extensive pathological changes, higher proportions of active and mixed lesions, and foamy microglia morphology. This pattern was positively correlated with more severe disease, the presence of B and T cells, and neuroaxonal damage. Scoring high on dimension 2 was associated with active lesions, reactive sites, and the presence of nodules. These donors had less severe disease, a specific pattern of cortical lesions, and MS risk variants in the human leukocyte antigen region, the latter indicating a connection between disease onset and this neuropathological dimension. Donors scoring high on dimension 3 showed increased lesional pathology with relatively more mixed and inactive lesions and ramified microglia morphology. This pattern was associated with longer disease duration, subpial cortical lesions, less involvement of the adaptive immune system, and less axonal damage. Taken together, the three dimensions may represent (1) demyelination and immune cell activity associated with pathological and clinical progression, (2) microglia (re)activity and possibly lesion initiation, and (3) loss of lesion activity and scar formation. Our findings highlight that a thorough understanding of the interplay between multiple pathological characteristics is crucial to understand the heterogeneity of MS pathology, as well as its association with genetic predictors and disease outcomes. The scores of donors on the dimensions can serve as an important starting point for further disentanglement of MS heterogeneity and translation into observations and interventions in living cohorts with MS.

Double Chromogen-based Immunohistochemical Staining: An Efficient Approach for Utilizing Long-term Formalin-fixed Tissue in Biobanks.

The New South Wales Brain Tissue Resource Centre is a human brain bank that provides top-quality brain tissue for cutting-edge neuroscience research spanning various conditions from alcohol use disorder to neurodegenerative diseases. However, the conventional practice of preserving brain tissue in formalin poses challenges for immunofluorescent staining primarily due to the formalin's tendency, over time, to create cross-links between antigens, which can obscure epitopes of interest. In addition, researchers can encounter issues such as spectral bleeding, limitations in using multiple colors, autofluorescence, and cross-reactivity when working with long-term formalin-fixed brain tissue. The purpose of the study was to test chromogen-based double immunolabeling to negate the issues with immunofluorescent staining. Colocalization of antigens was explored using chromogens 3-amino-9-ethylcarbazole (AEC) and 3,3,-diaminobenzidine in a sequential staining procedure where the AEC signal was eliminated by alcohol treatment. Combinations of 2 or 3 primary antibodies from the same or different species were trialed successfully with this protocol. The colocalization of antigens was also demonstrated with pseudocoloring that mimicked immunofluorescence staining. This staining technique increases the utility of archival formalin-fixed tissue samples.

A cell bank paradigm for preclinical evaluation of an analogous cellular product for an allogeneic cell therapy.

Toward the translation of allogeneic cell therapy products, cell banks are needed not only to manufacture the final human product but also during the preclinical evaluation of an animal-based analogous cellular product (ACP). These cell banks need to be established at both the master cell bank (MCB) level and the working cell bank (WCB) level. Inasmuch as most of the development of cell therapy products is at academic centers, it is imperative that academic researchers understand how to establish MCBs and WCBs within an academic environment. To illustrate this process, using articular cartilage as the model, a cell bank for an ACP was developed (MCBs at passage 2, WCBs at passage 5) to produce self-assembled neocartilage for preclinical evaluation (constructs at passage 7). The cell bank system is estimated to be able to produce between 160 000 and 400 000 constructs for each of the six MCBs. Overall, the ACP cell bank yielded constructs that are analogous to the intended human product, which is critical toward conducting preclinical evaluations of the ACP for inclusion in an Investigational New Drug application to the FDA.

Urgent Need for Regulatory Oversight of Human Cells, Tissues, and Cellular and Tissue-Based Products.

This Viewpoint discusses the death of a patient caused by unregulated biological products and efforts to encourage federal government oversight of such products.

A comparative review of human milk banking and national tissue banking programs.

This paper explores the legislative and operational commonalities and differences in Medical Products of Human Origin (MPHO) programs, including blood, hematopoietic cells, tissues and reproductive cells and human milk banking. The analysis includes ethical principles in donation and utilization, policies and legislation, public awareness and education, registries, guidelines in donor selection, safety and quality assurance, operational models and funding, infrastructure and human resources and biovigilance and evaluation of outcomes. Unlike other MPHO, the need for donor human milk (DHM) may be greatly reduced, that is, by ensuring optimal support for maternal lactation and breastfeeding. This should not be lost in the drive for wider and improved service provision. Nevertheless, increased overall demand for DHM is expected as a result of forthcoming international recommendations and also its increased use as the first-choice supplement to a mother's own milk both within and beyond preterm, low-birthweight and sick infant populations. Insight into current human milk banking highlights differences and gaps in practices that can benefit from further exploration and harmonization. Strong similarities with the ethical and operational principles underpinning donation and processing of the diverse MPHO suggest that legislating human milk banks within similar MPHO frameworks may bring additional safety and facilitate improved product quality. Moreover, that MPHO-inspired models operating within attainable regulatory requirements may contribute to sustainable human milk banking activity and growth.

Availability of individual proteins for quantitative analysis in postmortem brains preserved in two different brain banks.

AIM: Postmortem brain research is necessary for elucidating the pathology of schizophrenia; an increasing number of studies require a combination of suitable tissue samples preserved at multiple brain banks. In this study, we examined whether a comparative study of protein expression levels can be conducted using postmortem brain samples preserved in different facilities. METHODS: We compared the demographic factors of postmortem brain samples preserved in two institutions and measured and compared the expression levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glial fibrillary acidic protein (GFAP) in the prefrontal cortex and superior temporal gyrus. GAPDH is generally used as a loading control for western blotting, and GFAP is considered as an astrocyte marker in the brain. RESULTS: We found significant differences between the two institutions in postmortem interval, age at death, and preservation time. To reduce the effects of these differences on our measurements, the parameters were set as covariates in our analyses of covariance. Subsequently, no differences in GAPDH and GFAP expression were found between institutions. CONCLUSIONS: When studies are conducted using brain samples preserved in different brain banks, differences in demographic factors should be carefully considered and taken into account by statistical methods to minimize their impact as much as possible. Since there was no significant difference in the protein expression levels of GAPDH and GFAP in either region between the two institutions that preserved the postmortem brains, we concluded that it is possible to perform protein quantitative analysis assuming that there is no effect of difference between two institutions.

Deriving life-course residential histories in brain bank cohorts: A feasibility study.

INTRODUCTION: The exposome is theorized to interact with biological mechanisms to influence risk for Alzheimer's disease but is not well-integrated into existing Alzheimer's Disease Research Center (ADRC) brain bank data collection. METHODS: We apply public data tracing, an iterative, dual abstraction and validation process rooted in rigorous historic archival methods, to develop life-course residential histories for 1254 ADRC decedents. RESULTS: The median percentage of the life course with an address is 78.1% (IQR 24.9); 56.5% of the sample has an address for at least 75% of their life course. Archivists had 89.7% agreement at the address level. This method matched current residential survey methodology 97.4% on average. DISCUSSION: This novel method demonstrates feasibility, reproducibility, and rigor for historic data collection. To our knowledge, this is the first study to show that public data tracing methods for brain bank decedent residential history development can be used to better integrate the social exposome with biobank specimens. HIGHLIGHTS: Public data tracing compares favorably to survey-based residential history. Public data tracing is feasible and reproducible between archivists. Archivists achieved 89.7% agreement at the address level. This method identifies residences for nearly 80% of life-years, on average. This novel method enables brain banks to add social characterizations.

Brain Banking in Dementia Studies.

It is now well-established practice in dementia that one clinical entity may be caused by various neurodegenerative disorders, each with different histopathological findings, whereas neuropathologically confirmed patients may have different, unusual, and atypical clinical manifestations.This inconsistency in dementia patients leads to neuropathological examination of cases, and neuropathological examination seems to be an inevitable part of dementia practice, at least until all clinical entities are properly identified for humans.Additionally, the development of disease-modifying therapies and confirmation of the actual accurate diagnosis of the neurodegenerative disease that the drug is thought to modify or act upon are of great importance for neuropathological evaluation in brain banks.Neuropathological processes coexisting among patients diagnosed with established clinical criteria or international guidelines have provided a new perspective in the context of drug development.Here, we review our routinely used methodology in the context of the brain banking process.

The impact of heart valve and partial heart transplant models on the development of banking methods for tissues and organs: A concise review.

Cryopreserved human heart valves fill a crucial role in the treatment for congenital cardiac anomalies, since the use of alternative mechanical and xenogeneic tissue valves have historically been limited in babies. Heart valve models have been used since 1998 to better understand the impact of cryopreservation variables on the heart valve tissue components with the ultimate goals of improving cryopreserved tissue outcomes and potentially extrapolating results with tissues to organs. Cryopreservation traditionally relies on conventional freezing, employing cryoprotective agents, and slow cooling to sub-zero centigrade temperatures; but it is plagued by the formation of ice crystals and cell damage upon thawing. Researchers have identified ice-free vitrification procedures and developed a new rapid warming method termed nanowarming. Nanowarming is an emerging method that utilizes targeted application of energy at the nanoscale level to rapidly rewarm vitrified tissues, such as heart valves, uniformly for transplantation. Vitrification and nanowarming methods hold great promise for surgery, enabling the storage and transplantation of tissues for various applications, including tissue repair and replacement. These innovations have the potential to revolutionize complex tissue and organ transplantation, including partial heart transplantation. Banking these grafts addresses organ scarcity by extending preservation duration while preserving biological activity with maintenance of structural fidelity. While ice-free vitrification and nanowarming show remarkable potential, they are still in early development. Further interdisciplinary research must be dedicated to exploring the remaining challenges that include scalability, optimizing cryoprotectant solutions, and ensuring long-term viability upon rewarming in vitro and in vivo.

Brain banking in the United States and Europe: Importance, challenges, and future trends.

In recent years, brain banks have become valuable resources for examining the molecular underpinnings of various neurological and psychological disorders including Alzheimer disease and Parkinson disease. However, the availability of brain tissue has significantly declined. Proper collection, preparation, and preservation of postmortem autopsy tissue are essential for optimal downstream brain tissue distribution and experimentation. Collaborations between brain banks through larger networks such as NeuroBioBank with centralized sample request mechanisms promote tissue distribution where brain donations are disproportionately lower. Collaborations between brain banking networks also help to standardize the brain donation and sample preparation processes, ensuring proper distribution and experimentation. Ethical brain donation and thorough processing enhances the responsible conduct of scientific studies. Education and outreach programs that foster collaboration between hospitals, nursing homes, neuropathologists, and other research scientists help to alleviate concerns among potential brain donors. Furthermore, ensuring that biorepositories accurately reflect the true demographics of communities will result in research data that reliably represent populations. Implementing these measures will grant scientists improved access to brain tissue, facilitating a deeper understanding of the neurological diseases that impact millions.

Challenges of Implementing a Human Multi-Tissue Bank in a Public Hospital in the Interior of São Paulo: Under the Light of the Quality Management System.

BACKGROUND: Human multi-tissue banks (HMTB) are important health institutions specialized in the capture, processing, and distribution of human tissues for transplants and research, aiming for safety and quality in the supply of their products, intended for reconstructive surgeries and injury repair, in addition to contributing to the advancement of research developed in regenerative medicine. This study aims to report and share the experience of implementing an HMTB, as well as creating an institution's own quality management system. METHODS: This is a descriptive study, an experience report type, which identifies historical aspects of an HMTB's actions in the 5 years of implementing and operating the service. RESULTS: Initially, a musculoskeletal tissue bank was established in collaboration with the Department of Orthopedics at the State University of Campinas, São Paulo, Brazil, in June 2018. In 2023, through a management model and associated technologies, the banks of human musculoskeletal and ocular tissues at the institution established the HC-UNICAMP Human Multi-tissue Bank. CONCLUSIONS: The implementation of the HMTB with modern and technological infrastructure, associated with the development and operation of the quality management system, allowed us to provide excellent organization of work processes, as well as obtain the necessary health license to begin activities. It is believed that this report can be an important source of information and recommendations applicable to the implementation of other human HMTBs.

Biological parameters for quality evaluation of allografts from the Brazilian National Institute of Traumatology and Orthopedics tissue bank.

Bone allografts are clinically used in a variety of surgical procedures, and tissue banks are responsible for harvesting, processing, quality testing, storing, and delivering these materials for transplantation. In tissue banks, the bone is processed for the removal of all organic content, remaining only the tissue structure (scaffold). However, several studies have shown that even after using different processing methods, viable cells, functional proteins, and DNA may still persist in the tissue, which constitute the main causes of graft rejection. Therefore, the objective of this study was to establish techniques and biological parameters for quality validation of allografts. To this end, we propose the use of 3 combined methods such as microscopy, histology, and molecular biology techniques to evaluate the quality of allografts harvested and processed by the Brazilian National Institute of Traumatology and Orthopedics (INTO) tissue bank according to the donation criteria of the Brazilian National Health Surveillance Agency and the Brazilian National Transplant System. Bone fragments from different processing stages showed no viable cells on histology, an intact extracellular matrix on scanning electron microscopy, and gradual reduction in DNA amount. Different techniques were used to demonstrate the quality of allografts produced by the INTO tissue bank and to establish biological parameters for ensuring the safety and quality of these products. Future studies need to be undertaken to assess and validate the efficacy of the decellularization process in larger bone grafts with diverse architectural configurations.

Allografts use in orthopedic surgery: trend change over the past 11 years from a regional tissue bank.

Allografts are the second most transplanted tissue in medicine after blood and are now increasingly used for both primary and revision surgery. Allografts have the advantages of lower donor site morbidity, availability of multiple grafts, and shorter operative time. The Banks represents the bridge between Donor and Recipient and guarantees the quality and safety of the distributed allografts Given the increasing interest in these tissues, a retrospective analysis of data collected from the Regional Musculoskeletal Tissue Bank registry over an 11-year period (2009-2019) was conducted. The statistical analyses used were the Shapiro-Wilk normality test and a Poisson regression model. From January 2009 to December 2019, a total of 14,199 musculoskeletal tissues stored in the Regional Musculoskeletal Tissue Bank were provided for surgical allograft procedures. In 2009, the number of allografts performed was 925; this figure has steadily increased to 1599 in 2019. Epiphyses were taken as the reference tissue with an almost constant trend over the period, while a significant increase was denoted for extensor mechanism allograft, ligaments, tendons and long bone corticals (p < 0.001), processed bone tissues had no change in trend (p = 0.841). There was also a gradual decrease in the rate of microbiological positivity, as determined by bacteriological and serological tests performed on the collected tissues. This phenomenon is due to improved sampling techniques and the training of a dedicated team. Thus, we have seen how the use of allografts in orthopedic surgery has increased over the past 11 years, uniformly in terms of tissue type, except for the noticeable increase in ligamentous tissue.

Last twenty-years activity of cardiovascular tissue banking in Barcelona.

The Barcelona Tissue Bank was established from the merge of two previous multi-tissue banks. Potential donors are screened by Donor Center staff and multi-tissue retrieval is performed by specialized own teams. Tissue processing and preservation is performed in clean room facilities by specialised personnel. After quality control of both donor and all tissues results, the heart valves and vascular segments are stored until medical request. The aim of this report is to present the cardiovascular tissue activity and retrospectively evaluate the outcomes of the changes performed in last 20 years. Cardiovascular tissue from 4088 donors was received, specifically 3115 hearts and 2095 vascular segments were processed and evaluated. A total of 48% of the aortic valves, 68% of the pulmonary valves and 75% of the vascular segments were suitable for transplant. The main reason for discarding tissue was macroscopic morphology followed by microbiological results, for both valves and arteries. Altogether, 4360 tissues were distributed for transplantation: 2032 (47%) vascular segments, 1545 (35%) pulmonary valves and 781 (18%) aortic valves. The most common indication for aortic valve surgery was the treatment of endocarditis, while for pulmonary valves, it was congenital malformation reconstruction. Vascular segments were mainly used for reconstruction after ischemia. During this period, a number of changes were made with the goal of enhancing tissue quality, safety and efficacy. These improvements were achieved through the use of a new antibiotic cocktail, increasing of donor age criteria and changing the microbiological control strategy.

The Landscape of US and Global Rare Tumor Research Programs: A Systematic Review.

Rare cancers and other rare nonmalignant tumors comprise 25% of all cancer diagnoses and account for 25% of all cancer deaths. They are difficult to study due to many factors, including infrequent occurrence, lack of a universal infrastructure for data and/or tissue collection, and a paucity of disease models to test potential treatments. For each individual rare cancer, the limited number of diagnosed cases makes it difficult to recruit sufficient patients for clinical studies, and rare cancer research studies are often siloed. As a result, progress has been slow for many of these cancers. While rare cancer research efforts have increased over time, the breadth of the research landscape is not known. A recent literature search revealed a sharp increase in rare tumor, and rare cancer publications began in the early 2000s. To identify rare cancer research efforts being conducted in the US and globally, we conducted an online search of rare tumor/rare cancer research programs and identified 76 programs. To gain a deeper understanding of these programs, we composed and conducted a survey to ask programs for details about their research efforts. Of the 42 programs contacted to complete the survey, 23 programs responded. Survey results show most programs are collecting clinical data, molecular data, and biospecimens, and many are conducting molecular analyses. This landscape analysis demonstrates that multiple rare cancer research efforts are ongoing, and the rare cancer community may benefit from collaboration among stakeholders to accelerate research and improve patient outcomes.