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Retrievable, replaceable, macroencapsulated pancreatic islet xenografts. Long-term engraftment without
1Rogosin Institute, Department of Biochemistry and Surgery, New York Hospital-Cornell Medical Center, New York.
Transplantation
|February 15, 1995
Summary
Novel macrobeads protect transplanted pancreatic islets from immune rejection, maintaining normal blood sugar levels in diabetic mice for over 170 days. This method offers a promising, potentially retrievable alternative to immunosuppression for islet cell transplantation.
Area of Science:
- Biomedical Engineering
- Transplantation Immunology
- Regenerative Medicine
Background:
- Successful islet cell transplantation requires preventing immune rejection and prolonging graft survival.
- Islet encapsulation offers an alternative to immunosuppression by isolating islets within artificial membranes.
- Developing effective encapsulation methods is crucial for advancing islet transplantation therapies.
Purpose of the Study:
- To develop and evaluate a novel macroencapsulation method for pancreatic islets using agarose, collagen, and Gelfoam.
- To assess the efficacy of these macrobeads in preventing rejection and maintaining function of xenogeneic islet grafts in diabetic mice.
- To determine the biocompatibility and potential for retrieval and retransplantation of the macroencapsulated islets.
Main Methods:
- Rat islets were macroencapsulated in hydrophilic macrobeads composed of agarose, collagen, and Gelfoam.
- Encapsulated xenogeneic islets were transplanted intraperitoneally into streptozotocin-induced diabetic mice.
- Graft survival, glycemic control (normoglycemia, glucose tolerance tests), and local tissue response were monitored post-transplantation.
- Macrobeads were retrieved at various time points to assess tissue reaction and potential for retransplantation.
Main Results:
- Encapsulated xenografts maintained normoglycemia for over 170 days in recipient mice.
- Recipient mice demonstrated normal glucose tolerance tests, indicating sustained islet function.
- Retrieved macrobeads showed no evidence of tissue reaction or local inflammation up to 103 days post-transplantation.
- Retrieved macrobeads were successfully retransplanted, maintaining function.
Conclusions:
- The developed agarose-collagen/Gelfoam macrobeads effectively protect islet xenografts from immune rejection.
- These macrobeads provide a suitable microenvironment for maintaining islet function in vivo.
- The retrievable and re-transplantable nature of these macrobeads suggests their potential suitability for clinical islet cell xenotransplantation.