Size-controlled insulin-secreting cell clusters.
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 40-120μm 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 40μm to 60μm, glucose stimulation results in a greater amount of insulin produced per cell; and (2) as the cluster size increases beyond 60μm, 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 100-120μm 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.
Joint Graduate Group in Bioengineering, University of California at San Francisco, San Francisco, CA 94158, USA.
Adam D
AD
Mendelsohn
Crystal
C
Nyitray
Mark
M
Sena
Tejal A
TA
Desai
D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D051381:Rats
D007328:Insulin