A5031755211- Pancreatic function and diabetes
- Diabetes Management and Research
- Diabetes and associated disorders
- Cannabis and Cannabinoid Research
- Organ Transplantation Techniques and Outcomes
- Metabolism, Diabetes, and Cancer
- Xenotransplantation and immune response
- Organ Donation and Transplantation
- 3D Printing in Biomedical Research
- Tissue Engineering and Regenerative Medicine
- Diet, Metabolism, and Disease
- Genetics and Neurodevelopmental Disorders
- Pluripotent Stem Cells Research
- Pancreatitis Pathology and Treatment
- RNA Interference and Gene Delivery
- Pancreatic and Hepatic Oncology Research
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Renal Transplantation Outcomes and Treatments
- Diabetes Treatment and Management
- Transplantation: Methods and Outcomes
- Liver Disease and Transplantation
- Endoplasmic Reticulum Stress and Disease
- Mesenchymal stem cell research
University of Arizona
2015-2024
University of Minnesota
2009-2024
W. M. Keck Foundation
2019
GTx (United States)
2009-2018
Giner (United States)
2018
University of Minnesota System
2009-2017
Twin Cities Orthopedics
2008-2011
Diabetes Foundation
2009-2011
University of Minnesota Medical Center
2011
Massachusetts Institute of Technology
2000-2010
We sought to determine the long‐term outcomes in type 1 diabetic recipients of intraportal alloislet transplants on a modified immunosuppressive protocol. Six with hypoglycemia unawareness received one two islet infusions. Induction therapy was antithymocyte globulin (ATG) plus etanercept for tumor necrosis factor‐α blockade. Recipients cyclosporine and everolimus maintenance immunosuppression first year posttransplant, mycophenolic acid or mycophenolate mofetil subsequently substituted...
The Collaborative Islet Transplant Registry (CITR) collects data on clinical islet isolations and transplants. This retrospective report analyzed 1017 isolation procedures performed for 537 recipients of allogeneic transplantation in 1999-2010. study describes changes donor variables by era factors associated with quantity quality final products. Donor body weight BMI increased significantly over the period (p<0.001). yield measures have improved time including equivalent (IEQ)/particle...
There is a need for simple, quantitative and prospective assays islet quality assessment that are predictive of transplantation outcome. The current state-of-the-art athymic nude mouse bioassay costly, technically challenging retrospective. In this study, we report on the ability 2 parameters characterizing human quality: (1) oxygen consumption rate (OCR), measure viable volume; (2) OCR/DNA, fractional viability, to predict diabetes reversal in mice. Results demonstrate probability increases...
Type 1 diabetes is caused by autoreactive T cell-mediated β cell destruction. Even though co-inhibitory receptor programmed death-1 (PD-1) restrains autoimmunity, the expression and regulation of its cognate ligands on remains unknown. Here, we interrogated cell-intrinsic death ligand-1 (PD-L1) in mouse human islets. We measured a significant increase level PD-L1 surface frequency
The optimal enzyme blend that maximizes human islet yield for transplantation remains to be determined. In this study, we evaluated eight different combinations (ECs) in an attempt improve yield. ECs consisted of purified, intact or truncated class 1 (C1) and 2 (C2) collagenases from Clostridium histolyticum (Ch), neutral protease (NP) Bacillus thermoproteolyticus rokko (thermolysin) Ch (ChNP).We report the results 249 isolations, including 99 deceased donors (research n=57, clinical n=42)...
A cell encapsulation system generates oxygen from carbon dioxide for self-oxygenation.
Anaplerotic flux into the Kreb's cycle is crucial for glucose-stimulated insulin secretion from pancreatic beta-cells. However, regulation of through various anaplerotic pathways in response to combinations physiologically relevant substrates and its impact on unclear. Because different anaplerosis generate distinct products, they may differentially modulate secretory response. To examine this question, we applied 13C-isotopomer analysis quantify three pathways: 1) pyruvate carboxylase...
Abstract Improvements in pancreatic islet transplantation for treatment of diabetes are hindered by the absence meaningful quality assessment methods. Oxygen consumption rate (OCR) has previously been used to assess organs and primary tissue transplantation. In this study, we describe characterize a stirred microchamber measuring OCR with small quantities islets. The device titanium body chamber volume about 200 µL is magnetically water jacketed temperature control. partial pressure (pO 2 )...
Objective: The aim of this study was to assess whether continuous diffusion oxygen improves healing in people receiving treatment for diabetic foot ulcers (DFU). Method: A double-blind, placebo control randomised receive either active (CDO) therapy using an CDO device, or a fully operational device without delivering oxygen. Patients were followed until closure 12 weeks. Patients, caretakers, treating physicians and independent evaluators blinded the arm. All patients received identical...
Islet transplantation is emerging as a treatment option for selected patients with type 1 diabetes. The limited human islet supply from cadavers and poor yield quality remain substantial impediments to progress in the field. Use of porcine islets holds great promise large-scale application transplantation. Consistent isolation dependent on advances pancreas procurement, preservation, isolation, requiring detailed knowledge pancreatic anatomy. primary aim this study was describe vascular...
Background. Purified tissue dissociation enzymes (TDEs) are critical to successful human islet isolation required for clinical transplantation, but little is known about the characteristics of key enzymes-class I (C1) and class II (C2) collagenase from Clostridium histolyticum-used in these procedures. Here, we show differences between C1 found purified products manufactured by three suppliers impact two on yield. Methods. Collagenase Roche, Serva/Nordmark (Uetersen, Germany), VitaCyte...
Graham ML, Bellin MD, Papas KK, Hering BJ, Schuurman H‐J. Species incompatibilities in the pig‐to‐macaque islet xenotransplant model affect transplant outcome: a comparison with allotransplantation. Xenotransplantation 2011; 18: 328–342. © 2011 John Wiley & Sons A/S. Abstract: Background: Porcine transplantation into diabetic non‐human primates is considered most relevant translational research supporting clinical application. Most studies have focused on immunosuppressive protocols,...
Abstract Porcine islet xenotransplantation is considered a potential cell‐based therapy for type 1 diabetes. It currently being evaluated in diabetic nonhuman primates ( NHP ) to assess safety and efficacy of the product. However, due variety distinct differences between respective species, including insulin secretory characteristics islets, suitability predictive value preclinical model extrapolation clinical setting remain critical issue. Islets isolated from human (n = 3), 2), adult pig...
Background Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes needed. In this paper we present data on the utility of an assay based cellular oxygen consumption rate (OCR) predicting autotransplant (IAT) insulin independence (II). IAT is attractive model for evaluating characterization regarding their II due absence confounding factors such as immune rejection immunosuppressant toxicity....
Scott, W. E. III; Avgoustiniatos, S.; Ferrer-Fabrega, J.; Weegman, B. P.; Kircner, V. A.; Anazawa, T.; Rizzari, M. D.; Kidder, L. Stein, S. Matsumoto, Stone, J. Suszynski, T. M.; Aasheim, C.; Hammer, E.; Balamurugan, A. N.; O'Brien, Murtaugh, Tempelman, Sutherland, D. Hering, Papas, K. Author Information
Islet autotransplantation (IAT) is used to preserve as much insulin-secretory capacity possible in patients undergoing total pancreatectomy for painful chronic pancreatitis. The enzyme dissociate the pancreas a critical determinant of islet yield, which correlated with posttransplant function. Here, we present our experience IAT procedures compare product data using new SERVA/Nordmark (SN group; n = 46) standard Liberase-HI (LH 40). Total yields (mean +/- deviation; 216,417 79,278 equivalent...
The islet size distribution in a preparation may contribute to transplant outcomes. At the same equivalent (IE) dose, larger islets exhibit poorer therapeutic value and this be because of oxygen diffusion limitations that worsen proportion size.To test hypothesis, we studied impact index (ISI) other product characteristics on outcomes after autotransplant (IAT) recipients receiving marginal dose (2000-4999 IEs per kg body weight) from January 1, 2009 June 11, 2012, at University Minnesota...
Abstract Optimal function of immunoisolated islets requires adequate supply oxygen to metabolically active insulin producing beta‐cells. Using mathematical modeling, we investigated the influence pO 2 on islet secretory capacity and evaluated conditions that could lead development tissue anoxia, modeled for a 300 μm in 500 microcapsule or planar, slab‐shaped macrocapsule. The was used assess part contributed secretion. Assuming macrocapsule with islet, consumption rate (OCR) 100–300 nmol min...