This work investigated the impact of implantation sites on the biocompatibility of alginate encapsulated pig islets. Non-diabetic rats were implanted with adult pig islets encapsulated in alginate either intraperitoneally (IP; n=25), subcutaneously (SC; n=37) or under the kidney capsule (KC; n=34). Capsule biocompatibility (retrieval rate, capsule diameter, degree of capsule broken and cellular overgrowth, CD68/CD3 staining) as well as islets viability and functionality were assessed until 30 days after transplantation. Implantation site did not significantly influence the biocompatibility of empty alginate capsules after transplantation (n=48). Most of the empty capsules (>90%) were retrieved after harvesting and were free of cellular overgrowth until day 30 post-transplantation. Three days after implantation, no significant difference for encapsulated pig islets was observed in terms of capsule biocompatibility and islet functionality in peritoneum, KC or subcutaneously. However, between days 5 and 30 after transplantation, explanted capsules from IP demonstrated a higher degree of broken capsules (>13%) and capsules with severe cellular overgrowth (>50%, CD68+ infiltration) than capsules removed from SC and KC (p<0.05). This was associated with a significant reduction of islet viability, insulin content and insulin secretion. In rats, the peritoneum site seems not appropriate for promoting the engraftment of encapsulated pig islets. Kidney subcapsular and subcutaneous spaces represent an interesting alternative.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.biomaterials.2006.01.028 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Enhanced Insulin Production From Porcine Islets: More Insulin, Less Islets.
Transpl Int
January 2025
Pôle de Chirurgie Expérimentale et Transplantation, Université Catholique de Louvain, Brussels, Belgium.
Clinical pancreatic islet xenotransplantation will most probably rely on genetically modified pigs as donors. Several lines of transgenic pigs carrying one and more often, multiple modifications already exist. The vast majority of these modifications aim to mitigate the host immune response by suppressing major xeno-antigens, or expressing immunomodulatory molecules that act locally at the graft site.
View Article and Find Full Text PDFWhat Genetic Modifications of Source Pigs Are Essential and Sufficient for Cell, Tissue, and Organ Xenotransplantation?
Transpl Int
December 2024
Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.
Xenotransplantation of porcine organs has made remarkable progress towards clinical application. A key factor has been the generation of genetically multi-modified source pigs for xenotransplants, protected against immune rejection and coagulation dysregulation. While efficient gene editing tools and multi-cistronic expression cassettes facilitate sophisticated and complex genetic modifications with multiple gene knockouts and protective transgenes, an increasing number of independently segregating genetic units complicates the breeding of the source pigs.
View Article and Find Full Text PDFPET imaging of GABA receptors in pancreatic islets by [C]flumazenil.
EJNMMI Res
December 2024
Department of Medical Cell Biology, Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Box 571, 75123, Uppsala, Sweden.
Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by a progressive β-cell destruction. There are no clinically established methods for quantifying endocrine cells of the pancreas and current knowledge is almost exclusively based on autopsy material and functional measurements. Based on the expression of the γ-aminobutyric acid A receptors (GABARs) in pancreatic islets and the fact that GABAR agonists are being explored as treatment for T1D, we hypothesized that the positron emission tomography (PET) tracer [C]flumazenil ([C]FMZ) could serve as a marker of the endocrine mass of the pancreas.
View Article and Find Full Text PDFA novel intravascular bioartificial pancreas device shows safety and islet functionality over 30 days in nondiabetic swine.
Am J Transplant
November 2024
Isla Technologies, Inc, San Carlos, California, USA. Electronic address:
In this study using a discordant, xenogeneic, transplant model we demonstrate the functionality and safety of the first stent-based bioartificial pancreas (BAP) device implanted endovascularly into an artery, harnessing the high oxygen content in blood to support islet viability. The device is a self-expanding nitinol stent that is coated with a bilayer of polytetrafluoroethylene that forms channels to hold islets embedded in a hydrogel. We completed a 1-month study in the nondiabetic swine model (N = 3) to test the safety of the device and to assess islet functionality after device recovery.
View Article and Find Full Text PDFPig Xenotransplantation in Beta Cell Replacement: Addressing Challenges and Harnessing Potential for Type 1 Diabetes Therapy.
Transpl Int
November 2024
Clinic Unit of Regenerative Medicine and Organ Transplants and Diabetes Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan, Italy.
Article Synopsis
- * It explores the compatibility of porcine islets with human glucose metabolism, their potential as a reliable source of beta cells, and the immunological challenges faced in xenotransplantation.
- * The discussion includes regulatory and ethical considerations surrounding the use of pig islets, emphasizing the importance of ongoing research and dialogue to address obstacles and promote their integration into T1D therapies.*
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!