Current status of islet xenotransplantation

Cell therapy for Type 1 diabetes (T1D) utilizing islet cell transplantation can successfully restore endogenous insulin production in affected patients. Islet cell engraftment and survival are conditional on the use of efficacious anti-rejection therapies and on the availability of healthy donor cells. The scarcity of healthy human donor pancreata is a limiting factor in providing sufficient tissue to meet the demand for islet transplantation worldwide. A potential alternative to the use of cadaveric human donor pancreases is the use of animal sourced islets.Pancreatic islets obtained from pigs have emerged as an alternative to human tissues due to their great availability, physiological similarities to human islets, including the time-tested use of porcine insulin in diabetic patients and the ability to genetically modify the donor source.The evolution of refined, efficacious immunosuppressive therapies with reduced toxicity, improvements in donor management and genetic manipulation of the donor have all contributed to facilitate long-term function in pre-clinical models of pig islet grafts in non-human primates.As clinical consideration for this option is growing, and trials involving the use of porcine islets have begun, more compelling experimental data suggest that the use of pig islets may soon become a viable, safe, effective and readily available treatment for insulin deficiency in T1D patients

Arguments against the requirement of a biological license application for human pancreatic islets: The position statement of the islets for us collaborative presented during the fda advisory committee meeting

The Food and Drug Administration (FDA) has been regulating human islets for allo-transplantation as a biologic drug in the US. Consequently, the requirement of a biological license application (BLA) approval before clinical use of islet transplantation as a standard of care procedure has stalled the development of the field for the last 20 years. Herein, we provide our commentary to the multiple FDA’s position papers and guidance for industry arguing that BLA requirement has been inappropriately applied to allogeneic islets, which was delivered to the FDA Cellular, Tissue and Gene Therapies Advisory Committee on 15 April 2021. We provided evidence that BLA requirement and drug related regulations are inadequate in reassuring islet product quality and potency as well as patient safety and clinical outcomes. As leaders in the field of transplantation and endocrinology under the “Islets for US Collaborative” designation, we examined the current regulatory status of islet transplantation in the US and identified several anticipated negative consequences of the BLA approval. In our commentary we also offer an alternative pathway for islet transplantation under the regulatory framework for organ transplantation, which would address deficiencies of in current system

Antimicrobial proteins and polypeptides in pulmonary innate defence

Inspired air contains a myriad of potential pathogens, pollutants and inflammatory stimuli. In the normal lung, these pathogens are rarely problematic. This is because the epithelial lining fluid in the lung is rich in many innate immunity proteins and peptides that provide a powerful anti-microbial screen. These defensive proteins have anti-bacterial, anti- viral and in some cases, even anti-fungal properties. Their antimicrobial effects are as diverse as inhibition of biofilm formation and prevention of viral replication. The innate immunity proteins and peptides also play key immunomodulatory roles. They are involved in many key processes such as opsonisation facilitating phagocytosis of bacteria and viruses by macrophages and monocytes. They act as important mediators in inflammatory pathways and are capable of binding bacterial endotoxins and CPG motifs. They can also influence expression of adhesion molecules as well as acting as powerful anti-oxidants and anti-proteases. Exciting new antimicrobial and immunomodulatory functions are being elucidated for existing proteins that were previously thought to be of lesser importance. The potential therapeutic applications of these proteins and peptides in combating infection and preventing inflammation are the subject of ongoing research that holds much promise for the future

An evaluation of the suitability of selected waste products in feeds for three fish species

Five types of aquatic food industry waste products (carp offal, carp roe, fish frames, trout offal and surimi processing waste) together with fish meal were evaluated for their suitability as potential fish meal replacements, partially or wholly, in diets for three species (rainbow trout, Murray cod and shortfin eel) cultured in Australia, using a number of criteria.The proximate composition of the ingredients on a dry matter basis including protein content, lipid and ash, varied considerably. The essential amino acid (EAA) contents of the waste products and fish meal decreased in the order: carp roe &gt; fish meal &gt; carp offal &gt; \u27surimi\u27 processing waste &gt; fish frames &gt; trout offal. The results of cluster analysis of A/E ratios of waste products and fish whole body fell within three clusters. The EAAI of whole body tissue of Murray cod, rainbow trout and Australian shortfin eel however, were closest to fish meal, followed by fish frame waste and/or \u27surimi\u27 waste. The results on A/E ratios and EAAI did not conform to the raw data on TAA and EAA. Therefore, the study emphasizes the need to have a multi-prong approach to determine the suitability of ingredients for incorporation into fish feeds.<br /

Donation after circulatory death is associated with increased fibrosis on 1‐year post‐transplant kidney allograft surveillance biopsy

AimThe use of kidneys donated after circulatory death (DCD) provides an invaluable expansion of the organ supply for transplantation. Here, we investigated the effect of DCD on fibrotic changes on 1 1‐year post 1‐transplant surveillance kidney allograft biopsy.MethodsRecipients of a deceased donor kidney transplant between 2013 and 2017 at a single institution, who survived 1 year and underwent surveillance biopsy, were included in the analysis (n = 333: 87 DCD kidneys, 246 kidneys donated after brain death [DBD]). Banff scores for interstitial fibrosis and tubular atrophy were summed as IFTA and compared between the groups.ResultsDCD and DBD groups were comparable for baseline characteristics. Delayed graft function was 39% in DCD versus 19% in DBD, P = .0002. Patient and graft survival were comparable for DCD and DBD cohorts. IFTA scores were higher in DCD compared to DBD (2.43±..13 vs. 2.01±..08, P = .0054). On multivariate analysis, the odds of IFTA > 2 in the DCD group was 2.5× higher (95%CI: 1.354.63) than in the DBD group. Within the DCD group, kidneys with IFTA > 2 had inferior 5‐year graft survival (P = .037).ConclusionCompared to DBD kidneys, DCD kidneys developed a greater degree of fibrotic changes on 1‐year post‐transplant surveillance biopsy, which affected graft longevity within the DCD cohort.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170896/1/ctr14399.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170896/2/ctr14399_am.pd