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A scalable human islet 3D-culture platform maintains cell mass and function long-term for transplantation.
Am J Transplant
February 2024
Department of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
Present-day islet culture methods provide short-term maintenance of cell viability and function, limiting access to islet transplantation. Attempts to lengthen culture intervals remain unsuccessful. A new method was developed to permit the long-term culture of islets.
View Article and Find Full Text PDFBioengineered omental transplant site promotes pancreatic islet allografts survival in non-human primates.
Cell Rep Med
March 2023
Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address:
The transplanting islets to the liver approach suffers from an immediate posttransplant loss of islets of more than 50%, progressive graft dysfunction over time, and precludes recovery of grafts should there be serious complications such as the development of teratomas with grafts that are stem cell-derived islets (SC-islets). The omentum features an attractive extrahepatic alternative site for clinical islet transplantation. We explore an approach in which allogeneic islets are transplanted onto the omentum, which is bioengineered with a plasma-thrombin biodegradable matrix in three diabetic non-human primates (NHPs).
View Article and Find Full Text PDFFeasibility and efficacy of combined pancreatic islet-lung transplantation in cystic fibrosis-related diabetes-PIM study: A multicenter phase 1-2 trial.
Am J Transplant
July 2022
Department of Endocrinology, Diabetes and Nutrition, Strasbourg University Hospital, France.
Cystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis (CF), and restoring metabolic control in these patients may improve their management after lung transplantation. In this multicenter, prospective, phase 1-2 trial, we evaluate the feasibility and metabolic efficacy of combined pancreatic islet-lung transplantation from a single donor in patients with CFRD, terminal respiratory failure, and poorly controlled diabetes. Islets were infused via the portal vein under local anesthesia, 1 week after lung transplantation.
View Article and Find Full Text PDFUse of Induced Pluripotent Stem Cells to Build Isogenic Systems and Investigate Type 1 Diabetes.
Front Endocrinol (Lausanne)
February 2022
Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.
Type 1 diabetes (T1D) is a disease that arises due to complex immunogenetic mechanisms. Key cell-cell interactions involved in the pathogenesis of T1D are activation of autoreactive T cells by dendritic cells (DC), migration of T cells across endothelial cells (EC) lining capillary walls into the islets of Langerhans, interaction of T cells with macrophages in the islets, and killing of β-cells by autoreactive CD8 T cells. Overall, pathogenic cell-cell interactions are likely regulated by the individual's collection of genetic T1D-risk variants.
View Article and Find Full Text PDFTrisected pancreas model for testing tissue dissociation enzyme combinations: a novel methodology for improving human islet yield for clinical islet transplantation.
J Diabetes Metab Disord
June 2020
Department of Surgery, Clinical islet cell laboratory, Cardiovascular Innovation Institute, University of Louisville, Louisville, KY USA.
Purpose: Human islet isolation requires a defined collagenase-protease enzyme combination for obtaining a successful islet yield. While different islet laboratories use different enzyme combinations, a systematic methodology to identify optimal enzyme combinations and their concentrations within a single donor pancreas has not been tested. In this study, we designed a trisected pancreas model to test efficacy of three clinical grade enzyme blends (VitaCyte, Roche, SERVA) within a single pancreas.
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