Size-controlled insulin-secreting cell clusters

摘要

The search for an effective cure for type I diabetes from the transplantation of encapsulated pancreatic β-cell clusters has so far produced sub-optimal clinical outcomes. Previous efforts have not controlled the size of transplanted clusters, a parameter implicated in affecting long-term viability and the secretion of therapeutically sufficient insulin. Here we demonstrate a method based on covalent attachment of patterned laminin for fabricating uniformly size-controlled insulin-secreting cell clusters. We show that cluster size within the range 40-120 μm in diameter affects a variety of therapeutically relevant cellular responses including insulin expression, content and secretion. Our studies elucidate two size-dependent phenomena: (1) as the cluster size increases from 40 μm to 60 μm, glucose stimulation results in a greater amount of insulin produced per cell; and (2) as the cluster size increases beyond 60 μm, sustained glucose stimulation results in a greater amount of insulin secreted per cell. Our study describes a method for producing uniformly sized insulin-secreting cell clusters, and since larger cluster sizes risk nutrient availability limitations, our data suggest that 100-120 μm clusters may provide optimal viability and efficacy for encapsulated β-cell transplants as a treatment for type I diabetes and that further in vivo evaluation is warranted.