Efforts to re-establish insulin independence in patients with T1D using the implantation of encapsulated pancreatic beta-cell clusters has so far produced sub-optimal clinical outcomes. Previous efforts have not controlled the size of implanted islet clusters, a factor known to affect their long-term viability and the secretion of therapeutically sufficient insulin levels. This research demonstrated a method of creating a scaffold using naturally occurring proteins for fabricating uniformly size-controlled insulin-secreting cell clusters. The size of implanted cell clusters could then be controlled from experiment to experiment. The research defined the relationship between beta cell cluster sizes and the amount of insulin secreted per cell. Results showed that beyond a certain size, larger cluster sizes risk nutrient availability limitations and therefore produce less insulin. These laboratory based experiments defined a narrow range for the optimal size of encapsulated and implanted beta cell clusters. This size range provided the best viability and insulin production. This method and optimal range identified must now be tested in animal models of T1D to confirm the value of these findings.
Ramifications for Individuals with T1D:
This study sheds new light on an important aspect of the success of beta cell encapsulation product concepts – the size of the beta cell clusters in the encapsulation device. Defining the optimal size for these encapsulated beta cell clusters should improve the function of encapsulation products as a beta cell replacement therapy for individuals with T1D without the use of chronic immunosuppression.
This study was funded in part by JDRF.
Investigators and Institutions:
This work was conducted by Dr. Tejal Desai and her colleagues at the University of California, San Francisco.
Mendelsohn AD, Nyitray C, Sena M, Desai TA. (2012) Size-controlled insulin-secreting cell clusters. Acta Biomater. 8(12):4278-84 (Epub 2012 Aug 14).