Templated Islet Cells and Small Islet Cell Clusters for Diabetes Treatment

Abstract

A population of small reaggregated islets or clusters engineered from individual islet cells and having improved characteristics as compared to native isolated islets.

We claim: 
     
         1 . A population of reaggregated islets, wherein at least 80% of said reaggregated islets have a diameter of less than 90 μm, the reaggregated islets have low diffusion barriers relative to native large islets, and wherein the reaggregated islets have high cell viability relative to native small and large islets, and wherein reaggregated islet insulin production is characterized by levels that are greater than native isolated islets. 
     
     
         2 . The population of  claim 1 , wherein a majority of said reaggregated islets are spherical, elongated, or asymmetrical. 
     
     
         3 . The population of  claim 1 , wherein said reaggregated islets comprise pancreatic alpha cells, pancreatic beta cells, and pancreatic delta cells. 
     
     
         4 . The population of  claim 1 , wherein the alpha, beta, and delta cells are organized in a random pattern with the cells dispersed throughout the reaggregated islet. 
     
     
         5 . The population of  claim 1 , wherein at least 85% of said reaggregated islets are viable. 
     
     
         6 . The population of  claim 1 , wherein said reaggregated islets comprise beta cells that produce insulin in greater amounts compared to beta cells isolated from native small islet or native large islets. 
     
     
         7 . The population of  claim 1 , wherein each reaggregated islet is formed by introducing individual islet cells into a divot comprising a sidewall and a curved bottom wall and having a diameter of between 100 and 200 μm and a depth of between 50 and 150 μm, and exposing the cells to culture conditions, said individual islet cells aggregating into said reaggregated islet. 
     
     
         8 . The population of  claim 1 , said reaggregated islets having an identical morphology to small native islets, wherein the reaggregated islets are spherical in shape with a capsule-like external surface surrounding said reaggregated islet. 
     
     
         9 . The population of  claim 1 , said reaggregated islets having approximately 10% higher viability than native small islets and approximately 40% higher viability than native large islets. 
     
     
         10 . The population of  claim 1 , said reaggregated islets further comprising an additive incorporated into the reaggregated islet. 
     
     
         11 . The population of  claim 10 , wherein said additive is selected from the group consisting of growth factors, immunomodulators, immunosuppressants, cytokines, chemokines, disease-modifying antirheumatic drugs, anti-inflammatories, and antibiotics. 
     
     
         12 . The population of  claim 10 , wherein said additive is selected from the group consisting of small molecules, peptides, proteins, antibodies, and nucleic acids. 
     
     
         13 . The population of  claim 1 , wherein said reaggregated islets have low diffusion barriers to oxygen and glucose.