| 1. |
- Eriksson, Olof, et al.
(author)
-
Positron Emission Tomography to Assess the Outcome of Intraportal Islet Transplantation
- 2016
-
In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 65:9, s. 2482-2489
-
Journal article (peer-reviewed)abstract
- No imaging methodology currently exists to monitor viable islet mass after clinical intraportal islet transplantation. We investigated the potential of the endocrine positron emission tomography (PET) marker [11C]5-hydroxytryptophan ([11C]5-HTP) for this purpose. In a preclinical proof-of-concept study, the ex vivo and in vivo [11C]5-HTP signal was compared with the number of islets transplanted in rats. In a clinical study, human subjects with an intraportal islet graft (n = 8) underwent two [11C]5-HTP PET and MRI examinations 8 months apart. The tracer concentration in the liver as a whole, or in defined hotspots, was correlated to measurements of islet graft function. In rat, hepatic uptake of [11C]5-HTP correlated with the number of transplanted islets. In human subjects, uptake in hepatic hotspots showed a correlation with metabolic assessments of islet function. Change in hotspot standardized uptake value (SUV) predicted loss of graft function in one subject, whereas hotspot SUV was unchanged in subjects with stable graft function. The endocrine marker [11C]5-HTP thus shows a correlation between hepatic uptake and transplanted islet function and promise as a tool for noninvasive detection of viable islets. The evaluation procedure described can be used as a benchmark for novel agents targeting intraportally transplanted islets.
|
|
| 2. |
- Korsgren, Erik, et al.
(author)
-
An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas
- 2016
-
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:4, s. 1004-1008
-
Journal article (peer-reviewed)abstract
- The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. lmmunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes.
|
|
| 3. |
- Ricordi, Camillo, et al.
(author)
-
National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial : Manufacture of a Complex Cellular Product at Eight Processing Facilities
- 2016
-
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:11, s. 3418-3428
-
Journal article (peer-reviewed)abstract
- Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed.
|
|
