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Browsing by Author "Kandeel, Fouad"
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Item 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 MedicineIslet 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.Item Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes(Oxford University Press, 2018-05-01) Aslamy, Arianne; Oh, Eunjin; Ahn, Miwon; Moin, Abu Saleh Md; Chang, Mariann; Duncan, Molly; Hacker-Stratton, Jeannette; El-Shahawy, Mohamed; Kandeel, Fouad; DiMeglio, Linda A.; Thurmond, Debbie C.; Cellular and Integrative Physiology, School of MedicineContext: Efforts to preserve β-cell mass in the preclinical stages of type 1 diabetes (T1D) are limited by few blood-derived biomarkers of β-cell destruction. Objective: Platelets are proposed sources of blood-derived biomarkers for a variety of diseases, and they show distinct proteomic changes in T1D. Thus, we investigated changes in the exocytosis protein, double C2 domain protein-β (DOC2B) in platelets and islets from T1D humans, and prediabetic nonobese diabetic (NOD) mice. Design, Patients, and Main Outcome Measure: Protein levels of DOC2B were assessed in platelets and islets from prediabetic NOD mice and humans, with and without T1D. Seventeen new-onset T1D human subjects (10.3 ± 3.8 years) were recruited immediately following diagnosis, and platelet DOC2B levels were compared with 14 matched nondiabetic subjects (11.4 ± 2.9 years). Furthermore, DOC2B levels were assessed in T1D human pancreatic tissue samples, cytokine-stimulated human islets ex vivo, and platelets from T1D subjects before and after islet transplantation. Results: DOC2B protein abundance was substantially reduced in prediabetic NOD mouse platelets, and these changes were mirrored in the pancreatic islets from the same mice. Likewise, human DOC2B levels were reduced over twofold in platelets from new-onset T1D human subjects, and this reduction was mirrored in T1D human islets. Cytokine stimulation of normal islets reduced DOC2B expression ex vivo. Remarkably, platelet DOC2B levels increased after islet transplantation in patients with T1D. Conclusions: Reduction of DOC2B is an early feature of T1D, and DOC2B abundance may serve as a valuable in vivo indicator of β-cell mass and an early biomarker of T1D.