Improved survival of microencapsulated islets during in vitro culture and enhanced metabolic function following transplantation

Abstract

Aims/hypothesis. The aim of this study was to determine whether a simple alginate capsule can prolong islet survival and function during long-term tissue culture. We also wanted to observe the ability of these encapsulated islets to restore glucose responsiveness to diabetic recipients, along with the quantity of islets required to do so. Methods. We compared the recovery and metabolic function of encapsulated canine islets with that of non-encapsulated canine islets following 1, 2 or 3 weeks of tissue culture. These culture preparations were also transplanted into diabetic nude mice and compared for their ability to reverse diabetes. Furthermore, short-term cultured encapsulated and nonencapsulated islets were transplanted in varying numbers to determine the minimum dose required to normalise blood glucose and prolong recipient survival.Results. Islet recovery following 1, 2 and 3 weeks of tissue culture was significantly higher when islets were encapsulated. When these islets were recovered at 1, 2 and 3 weeks and transplanted into diabetic nude mice, survival at 100 days was 100% for all encapsulated groups, versus 66%, 33% and 33% respectively for the non-encapsulated islets. Additionally, substantially fewer short-term cultured islets were required to normalise blood glucose when the islets were encapsulated. Recipients of encapsulated islets also had significantly longer survival times than recipients of non-encapsulated preparations. Conclusions/interpretation. This study demonstrates that encapsulation of islets with purified alginate improves islet survival and function in vitro and in vivo.

Nanotechnology for regenerative medicine

“…This strategy has provided a wide range of promising therapeutic treatments for central nervous system diseases (Borlongan et al 2004), diabetes (Korbutt et al 2004), hemophilia (Hortelano et al 1996), and anemia (Rinsch et al 2002) among others. This technology offers a safe and manufacturable method for the local and systemic delivery of therapeutic molecules from the enclosed cells.…”

Dental Stem Cell Differentiation Toward Endodermal Cell Lineages: Approaches to Control Hepatocytes and Beta Cell Transformation

“…The material for encapsulation can be brown algae derived alginate which is currently being used in clinical trials [ 134 ]. Another material, polysulphone can also be utilized but it needs to be modifi ed in order to reduce insulin adsorption [ 135 ].…”

Direct effect of alginate purification on the survival of islets immobilized in alginate-based microcapsules

“…Moreover, Korbutt et al [9] have shown that immobilizing islets in alginate beads improves islet cell survival in vitro and in vivo. In the latter case, the improvement was not due to immunoprotection, since the experiments were conducted in either immuno-incompetent animals (NUDE mice) or a model of syngeneic transplantation.…”