Long-Term Graft Function of Adult Rat and Human Islets Encapsulated in Novel Alginate-Based Microcapsules After Transplantation in Immunocompetent Diabetic Mice

Abstract

We describe the results of the first study to show that adult rat and human islets can be protected against xenogenic rejection in immunocompetent diabetic mice by encapsulating them in a novel alginate-based microcapsule system with no additional permselective membrane. Nonencapsulated islets lost function within 4 -8 days after being transplanted into diabetic Balb/c mice, whereas transplanted encapsulated adult rat or human islets resulted in normoglycemia for >7 months. When rat islet grafts were removed 10 and 36 weeks after transplantation, the mice became immediately hyperglycemic, thus demonstrating the efficacy of the encapsulated islets. The explanted capsules showed only a mild cellular reaction on their surface and a viability of >85%, and responded to a glucose stimulus with a 10-fold increase in insulin secretion. Furthermore, transplanted mice showed a slight decrease in the glucose clearance rate in response to intraperitoneal glucose tolerance tests 3-16 weeks after transplantation; after 16 weeks, the rate remained stable. Similar results were obtained for encapsulated human islets. Thus we provide the first evidence of successful transplantation of microencapsulated human islets. In conclusion, we have developed a novel microcapsule system that enables survival and function of adult rat and human islets in immunocompetent mice without immunosuppression for >7 months. Diabetes 54:687-693, 2005

Prevention of Osteoporosis in Mice after Ovariectomy via Allograft of Microencapsulated Ovarian Cells

“…It has been reported that some hormone-secreting cells such as islet cells, dopaminergic cells, and parathyroid cells have been successfully microencapsulated and transplanted (Schneider et al, 2005). In this study, allotransplanted microencapsulated ovarian cells improved bone characteristics in OVX mice.…”

Nano-scale encapsulation enhances allograft survival and function of islets transplanted in a mouse model of diabetes

“…A long-term study of the function and graft survival with this multilayer coating scheme has not yet been performed. Nevertheless, unlike the arguably more expected durability of alginate microcapsules [15,42], the nano-layers used in this study, while being non-biodegradable, are not expected or intended to last for many months under in vivo conditions. Rather, we propose that nano-scale encapsulation is an alternative technology that may promote engraftment by allowing intraportal administration and by limiting early islet loss caused by exposure to an inflammatory environment.…”

“…Previous studies in animal models [8,9] and in human participants [10,11] have demonstrated that physical isolation of islets from the host immune system by, for example, alginate microencapsulation is effective in preventing beta cell loss and in maintaining long-term secretory function in transplanted allogeneic and xenogeneic islets without systemic immunosuppression [12][13][14][15][16]. Although conferring the immunological advantages predicted from graft/host isolation, microcapsules have some significant drawbacks.…”

Living Cell Factories ‐ Electrosprayed Microcapsules and Microcarriers for Minimally Invasive Delivery

“…In this way, 'living cell factory' systems can be delivered through microencapsulation for therapies such as diabetes, back pain, bone healing and osteoarthritis in a cost-effective manner. One study demonstrated that microcapsules made up of ultrahigh−viscosity alginate cross-linked with Ba 2+ and stabilized with human serum albumin (HSA) protect adult rat and human islets against xenorejection after transplantation [48] .…”