Browsing by Subject "Islet transplantation"

Now showing 1 - 3 of 3
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    Advancing Treatment for Pancreatitis: A Prospective Observational Study of TPIAT (POST Study). Protocol, Manual of Procedures, and Case Report Forms
    (2024-08-08) Bellin, Melena; post@umn.edu; POST, Staff Members; University of Minnesota Division of Pediatric Endocrinology and Division of Biostatistics and Health Data Science
    This "dataset" contains supplemental materials only: the final version of the POST Study's protocol, Manual of Procedures (MOP), and Case Report Forms (CRFs), for reference generally and specifically for the public-use datasets, which will be made available after the primary publications appear. Please contact POST study staff at post@umn.edu to request access to the actual data.
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    Development and Validation of a Multinuclear Magnetic Resonance Spectroscopy Toolkit for Bioartificial Pancreas Assessment
    (2016-06) Einstein, Samuel
    Type 1 diabetes is a devastating disease with increasing incidence and prevalence. Insulin therapy, while life-saving, does not prevent severe complications that substantially increase both morbidity and mortality. Whole pancreas and pancreatic islet transplantation are treatments for diabetes, but favorable long-term outcomes are inconsistent and the procedures are restricted to a small group of patients due to a variety of limitations. These impediments include the current demand for donor pancreata far exceeding supply, allotransplantation requiring a lifetime of immunosuppression, and premature graft failure. Macroencapsulated tissue-engineered grafts (TEGs) may mitigate or eliminate these limitations by allowing the use of alternative cell sources (such as porcine or stem-cell-derived islets), providing immunoisolation, and encourage graft survival through therapeutic interventions. TEGs possess great potential, but require significant development to fulfill their promise of a safe, effective, and definitive cure for type 1 diabetes. To enable and expedite TEG development, novel techniques to assess oxygen status (pO₂) and viability were developed, validated, and applied. Hypoxia is currently the most significant obstruction preventing widespread utilization of TEGs, rendering measurements of TEG pO₂ critically necessary. Fluorine-19 magnetic resonance spectroscopy (¹⁹F-MRS) was adapted for in vivo pO₂ measurement in TEGs and validated with a well-established technique. It was found that ¹⁹F-MRS can be a robust, accurate, and noninvasive technique to monitor TEG pO₂ for long durations post-implantation. This technique was applied to the murine model and demonstrated that TEGs implanted subcutaneously experience hypoxia unconducive to supporting islet viability and function. Therefore, a method for the delivery of supplemental oxygen (DSO) to increase in vivo pO₂ was developed and its efficacy was evaluated with ¹⁹F-MRS. It was found that DSO can successfully increase the pO₂ of macroencapsulated TEGs and enhance islet survival. While providing crucial information, measuring pO₂ does not necessarily correlate to islet viability, necessitating the development of additional techniques. Islet viability was first assessed by measuring pO₂ with ¹⁹F-MRS and calculating the oxygen consumption rate (OCR) using a mathematical model. Finally, to facilitate in vivo viability assessment and increase measurement accuracy, oxygen-17 MRS was developed to directly measure and noninvasively quantify the OCR of TEGs.
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    Increasing the applicability of transplantation tolerance in solid organs by leveraging linked suppression
    (2022-11) Finn, Sade
    Objectives: To investigate differences in immune responsiveness of islet allograft recipients before and after ADL infusion-based tolerance protocol. To understand the implications of MHC-I and MHC-II matching on linked suppression.Methodology: Peripheral blood mononuclear cells were collected from a cohort of 5 nonhuman primates who underwent islet transplantation after two peritransplant infusions of apoptotic donor leukocytes under the cover of short-term immunotherapy with anti-CD40 antibody, rapamycin, soluble tumor necrosis factor receptor and anti-IL-6R antibody between posttransplant day 60 and 90. Recipient PBMCs were cocultured with irradiated donor PBMC from the tolerized islet donor DR matched to the recipient (Donor DR Match), unrelated class I MHC allele matched donor (3P Class I Match), unrelated class II MHC allele matched donor (3P Class II Match), and unrelated MHC complete mismatched donor (Complete Mismatch) in a 5-day mixed leukocyte reaction. Both flow cytometry and cytometry by time of flight were used for data acquisition. Results: When recipient PBMCs treated with ADL infusion and short course immunotherapy was challenged with third-party antigen matched at either MHC-I (3P Class I) or MHC-II (3P Class II) to Donor DR, we again observed a near 2-fold increase in the Treg and Tr1 populations, providing evidence of linked suppression. Both third-party MHC matched conditions were associated with an increase in regulatory CD4 cell subsets and decreased CD4 and CD8 effector T cells compared to challenge with complete mismatched antigen. Conclusion: For the first time, we demonstrate linked suppression in a large animal model. Our study pointed to a slight trend of class II MHC matching showing greater expansion of Treg population compared to class I MHC matching that was consistent with the literature.