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London, Canada

Sernova Corporation | Date: 2015-02-18

Devices and methods for transplanting cells in a host body are described. The cell comprises a porous scaffold that allows ingrowth of vascular and connective tissues, a plug or plug system configured for placement within the porous scaffold, and a seal configured to enclose a proximal opening in the porous scaffold. The device may further comprise a cell delivery device for delivering cells into the porous scaffold. The method of cell transplantation comprises a two step process. The device is incubated in the host body to form a vascularized collagen matrix around a plug positioned within the porous scaffold. The plug is then retracted from the porous scaffold, and cells are delivered into the vascularized space created within the porous scaffold.

Pepper A.R.,University of Western Ontario | Pepper A.R.,Sernova Corporation | Welch I.,University of Western Ontario | Bruni A.,Sernova Corporation | And 4 more authors.

OBJECTIVE: A stringent porcine islet autograft diabetes model was developed to enable the assessment of autoislet safety and efficacy in either portal vein or an extrahepatic site. METHODS: A 95% pancreatectomy was performed preserving the pancreaticoduodenal arcade; however, glycemic control was still maintained at 3.3 ± 0.3 days (mean ± SEM), shown by euglycemic fasting blood glucose levels of 4.9 ± 0.8 mmol/L (mean ± SEM, n = 3). To reduce surgical complications and eliminate remaining islets, pigs were dosed intravenously after a modified 90% pancreatectomy, with 150-mg/kg streptozotocin, producing a diabetic state (18.9 ± 1.8 mmol/L [mean ± SEM], n = 8; P < 0.001) within 2.0 ± 0.9 days (mean ± SEM). RESULTS: Animals presented with sustained hyperglycemia, failing a glucose challenge test 12 weeks after diabetic induction, and showed no stimulated C-peptide secretion compared to nondiabetic controls (baseline: 0.479 ± 0.080 ng/mL [mean ± SEM] vs after procedure: 0.219 ± 0.055 ng/mL [mean ± SEM], P = 0.02). Diabetic animals were maintained on daily insulin. Despite an initial decline in body weight acutely after pancreatectomy and streptozotocin administration, the mean body weight increased after induction over the approximately 88-day study, indicating that the animals were in good health. CONCLUSION: This stringent porcine model of diabetic induction should be used to assess autograft transplantation safety and efficacy. Copyright © 2013 Lippincott Williams & Wilkins. Source

Pepper A.R.,University of Alberta | Pawlick R.,University of Alberta | Gala-Lopez B.,University of Alberta | MacGillivary A.,Sernova Corporation | And 4 more authors.

Background. Islet transplantation is a successful â-cell replacement therapy for selected patients with type 1 diabetes mellitus. Although high rates of early insulin independence are achieved routinely, long-termfunction wanes over time. Intraportal transplantation is associated with procedural risks, requiresmultiple donors, and does not afford routine biopsy. Stem cell technologiesmay require potential for retrievability, and graft removal by hepatectomy is impractical. There is a clear clinical need for an alternative, optimized transplantation site. The subcutaneous space is a potential substitute, but transplantation of islets into this site has routinely failed to reverse diabetes. However, an implanted device, which becomes prevascularized before transplantation, may alter this equation.Methods. Syngeneic mouse islets were transplanted subcutaneously within Sernova Corp's Cell Pouch (CP). All recipients were preimplanted with CPs 4 weeks before diabetes induction and transplantation. After transplantation, recipients were monitored for glycemic control and glucose tolerance. Results. Mouse islets transplanted into the CP routinely restored glycemic control with modest delay and responded well to glucose challenge, comparable to renal subcapsular islet grafts, despite a marginal islet dose, and normoglycemia was maintained until graft explantation. In contrast, islets transplanted subcutaneously alone failed to engraft. Islets within CPs stained positively for insulin, glucagon, and microvessels. Conclusions. The CP is biocompatible, forms an environment suitable for islet engraftment, and offers a potential alternative to the intraportal site for islet and future stem cell therapies. © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source

Kriz J.,University of Western Ontario | Vilk G.,University of Western Ontario | Vilk G.,London Health Sciences Center | Vilk G.,Sernova Corporation | And 8 more authors.
American Journal of Surgery

Background: The greater omentum with its vascularization and blood flow has been considered as a location for islet transplantation; however, there is a need to provide a controlled and protected site for the islets within the omentum that would be applicable to donor islets and future stem cell technologies. Here we describe the use of a novel device implanted within the omentum with a subcutaneous delivery port that offers an environment for donor islets. Methods: A prototype cell pouch device was wrapped in the greater omentum and an islet implantation port was exposed subcutaneously in diabetic Lewis rats. After tissue growth throughout the device, islet isografts were implanted and long-term glucose control was evaluated. Results: By using this technique, 7 of 10 diabetic rat recipients showed long-term normal blood glucose levels after minimal islet dose transplants. Histologic assessment revealed collagen formation and vascularization within the device. Conclusions: The implanted device assessed using this technique provides a safe and efficacious environment for the support of pancreatic islets contained within a removable device as a cell therapy in a highly vascularized setting. © 2012 Elsevier Inc. All rights reserved. Source

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