Economics of Beta-Cell Replacement Therapy.

PURPOSE OF REVIEW: Type 1 diabetes impacts 1.3 million people in the USA with a total direct lifetime medical cost of $133.7 billion. Management requires a mix of daily exogenous insulin administration and frequent glucose monitoring. Decision-making by the individual can be burdensome. RECENT FINDINGS: Beta-cell replacement, which involves devices protecting cells from autoimmunity and allo-rejection, aims at restoring physiological glucose regulation and improving clinical outcomes in patients. Given the significant burden of T1D in the healthcare systems, cost-effectiveness analyses can drive innovation and policymaking in the area. This review presents the health economics analyses performed for donor-derived islet transplantation and the possible outcomes of stem cell-derived beta cells. Long-term cost-effectiveness of islet transplantation depends on the engraftment of these transplants, and the expenses and thresholds assumed by healthcare systems in different countries. Early health technology assessment analyses for stem cell-derived beta-cell replacement suggest manufacturing optimization is necessary to reduce upfront costs.

Transplantation of Macroencapsulated Insulin-Producing Cells.

PURPOSE OF REVIEW: There is considerable interest in using macroencapsulation devices as a delivery strategy for transplanting insulin-producing cells. This review aims to summarize recent advances, to highlight remaining challenges, and to provide recommendations for the field. RECENT FINDINGS: A variety of new device designs have been reported to improve biocompatibility and to provide protection for islet/beta cells from immune destruction while allowing continuous secretion of insulin. Some of these new approaches are in clinical trials, but more research is needed to determine how sufficient beta-cell mass can be transplanted in a clinically applicable device size, and that insulin is secreted with kinetics that will safely provide adequate controls of glucose levels. Macroencapsulation is a potential solution to transplant beta cells without immunosuppression in diabetes patients, but new strategies must be developed to show that this approach is feasible.

Rat liver sinusoidal endothelial cells survive without exogenous VEGF in 3D perfused co-cultures with hepatocytes.

Liver sinusoidal endothelial cells (SECs) are generally refractory to extended in vitro culture. In an attempt to recreate some features of the complex set of cues arising from the liver parenchyma, we cocultured adult rat liver SECs, identified by the expression of the marker SE-1, with primary adult rat hepatocytes in a 3D culture system that provides controlled microscale perfusion through the tissue mass. The culture was established in a medium containing serum and VEGF, and these factors were then removed to assess whether cells with the SE-1 phenotype could be supported by the local microenvironment in vitro. Rats expressing enhanced green fluorescent protein (EGFP) in all liver cells were used for isolation of the SE-1-positive cells added to cocultures. By the 13th day of culture, EGFP-expressing cells had largely disappeared from 2D control cultures but exhibited moderate proliferation in 3D perfused cultures. SE-1-positive cells were present in 3D cocultures after 13 days, and these cultures also contained Kupffer cells, stellate cells, and CD31-expressing endothelial cells. Global transcriptional profiling did not reveal profound changes between 2D and 3D cultures in expression of most canonical angiogenic factors but suggested changes in several pathways related to endothelial cell function.