Browsing by Subject "Islet transplantation"

Now showing 1 - 5 of 5
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    Circulating Unmethylated Insulin DNA As a Biomarker of Human Beta Cell Death: A Multi-laboratory Assay Comparison
    (Endocrine Society, 2020-03-01) Speake, Cate; Ylescupidez, Alyssa; Neiman, Daniel; Shemer, Ruth; Glaser, Benjamin; Tersey, Sarah A.; Usmani-Brown, Sahar; Clark, Pamela; Wilhelm, Joshua J.; Bellin, Melena D.; Herold, Kevan C.; Mirmira, Raghavendra G.; Dor, Yuval; Evans-Molina, Carmella; Pediatrics, School of Medicine
    Context: There is an unmet need for biomarkers of pancreatic beta-cell death to improve early diagnosis of type 1 diabetes, enroll subjects into clinical trials, and assess treatment response. To address this need, several groups developed assays measuring insulin deoxyribonucleic acid (DNA) with unmethylated CpG sites in cell-free DNA. Unmethylated insulin DNA should be derived predominantly from beta-cells and indicate ongoing beta-cell death. Objective: To assess the performance of three unmethylated insulin DNA assays. Design and participants: Plasma or serum samples from 13 subjects undergoing total pancreatectomy and islet autotransplantation were coded and provided to investigators to measure unmethylated insulin DNA. Samples included a negative control taken post-pancreatectomy but pretransplant, and a positive control taken immediately following islet infusion. We assessed technical reproducibility, linearity, and persistence of detection of unmethylated insulin DNA for each assay. Results: All assays discriminated between the negative sample and samples taken directly from the islet transplant bag; 2 of 3 discriminated negative samples from those taken immediately after islet infusion. When high levels of unmethylated insulin DNA were present, technical reproducibility was generally good for all assays. Conclusions: The measurement of beta cell cell-free DNA, including insulin, is a promising approach, warranting further testing and development in those with or at-risk for type 1 diabetes, as well as in other settings where understanding the frequency or kinetics of beta cell death could be useful.
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    The demise of islet allotransplantation in the United States: A call for an urgent regulatory update
    (Wiley, 2021-04) Witkowski, Piotr; Philipson, Louis H.; Kaufman, Dixon B.; Ratner, Lloyd E.; Abouljoud, Marwan S.; Bellin, Melena D.; Buse, John B.; Kandeel, Fouad; Stock, Peter G.; Mulligan, David C.; Markmann, James F.; Kozlowski, Tomasz; Andreoni, Kenneth A.; Alejandro, Rodolfo; Baidal, David A.; Hardy, Mark A.; Wickrema, Amittha; Mirmira, Raghavendra G.; Fung, John; Becker, Yolanda T.; Josephson, Michelle A.; Bachul, Piotr J.; Pyda, Jordan S.; Charlton, Michael; Millis, J. Michael; Gaglia, Jason L.; Stratta, Robert J.; Fridell, Jonathan A.; Niederhaus, Silke V.; Forbes, Rachael C.; Jayant, Kumar; Robertson, R. Paul; Odorico, Jon S.; Levy, Marlon F.; Harland, Robert C.; Abrams, Peter L.; Olaitan, Oyedolamu K.; Kandaswamy, Raja; Wellen, Jason R.; Japour, Anthony J.; Desai, Chirag S.; Naziruddin, Bashoo; Balamurugan, Appakalai N.; Barth, Rolf N.; Ricordi, Camillo; Surgery, School of Medicine
    Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and “more than minimally manipulated” human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as “minimally manipulated tissue” and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.
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    Islet or pancreas after kidney transplantation: Is the whole still greater than some of its parts?
    (Elsevier, 2021) Fridell, Jonathan A.; Stratta, Robert J.; Surgery, School of Medicine
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    Mouse models and human islet transplantation sites for intravital imaging
    (Frontiers Media, 2022-10-05) Wagner, Leslie E.; Melnyk, Olha; Duffett, Bryce E.; Linnemann, Amelia K.; Biochemistry and Molecular Biology, School of Medicine
    Human islet transplantations into rodent models are an essential tool to aid in the development and testing of islet and cellular-based therapies for diabetes prevention and treatment. Through the ability to evaluate human islets in an in vivo setting, these studies allow for experimental approaches to answer questions surrounding normal and disease pathophysiology that cannot be answered using other in vitro and in vivo techniques alone. Intravital microscopy enables imaging of tissues in living organisms with dynamic temporal resolution and can be employed to measure biological processes in transplanted human islets revealing how experimental variables can influence engraftment, and transplant survival and function. A key consideration in experimental design for transplant imaging is the surgical placement site, which is guided by the presence of vasculature to aid in functional engraftment of the islets and promote their survival. Here, we review transplantation sites and mouse models used to study beta cell biology in vivo using intravital microscopy and we highlight fundamental observations made possible using this methodology.