Enhancing Viability
and Function of Isolated Islets in vitro via Controlled
Reaggregation and Introduction of Matrix Proteins
The islets of Langerhans (islets) are cell aggregates in the
pancreas containing mostly beta-cells, the insulin-producing cells that maintain
healthy glucose levels in the body. Islets are naturally heterogeneous in size
ranging from less than 50 micrometers in diameter to more than 350 micrometers
and are supported in vivo by a dense capillary network that facilitates
nutrient and waste transport to and from the cell cluster. When islets are
isolated from donors for use in transplantation procedure for the treatment of
Type I diabetes mellitus, however, it is necessary to remove the capillary
network to reduce immune response from the host patient. Removing this vascular
network also changes the mode in which the cells of the islet receive nutrients
and eliminate waste. When the vasculature is removed from the islet, it becomes
apparent that islet size plays a role in function and viability inside of the
cell cluster. It has been shown in vitro that smaller islets (less than
150 micrometers in diameter) produce more insulin on a per-cell basis than
larger islets and maintain higher levels of viability. It is unspecified,
however, which aggregate size is ideal for optimal beta-cell survival and
function.
The aim of my project is to reproducibly control islet aggregation in vitro
and determine the optimal aggregate size based on cell viability and function.
Once the ideal islet size is determined, extra-cellular matrix proteins and
growth factors will be introduced to the microenvironment experienced by the
aggregates in vitro to increase survival rate and insulin secretion.
Ultimately, an understanding of these parameters can be used to increase the
success rate of transplantation of islets for the treatment of Type I diabetes
in vivo.
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