Chenodeoxycholic Acid to Examine Cellular Viability and Functions

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Significantly greater cell viability (p < 0.01) was brought about by Chenodeoxycholic Acid(CDCA) incorporation which optimised microencapsulated cell survival compared with the F1 control microcapsules, but overall cell viability still
remained low,<50 %. After normalising for cell count, Table 1 shows more insulin production (p< 0.01) brought about by CDCA, which suggests a direct biological effect by CDCA on β-cells. There was a significant increase in cell respiration, metabolism, bioenergetics and energy production brought about by CDCA incorporation into the microcapsules. The increase in the metabolic biomarkers’ basal respiration, maximal respiration, ATP production and glycolysis suggest intracellular activation and enhanced inner-membrane mitochondrial production of ATP brought about by CDCA. The biological and inflammatory show levels of TNF-α, IFN-γ, IL-6 and IL-1β. The incorporation of CDCA into the microcapsules brought about a significant reduction in all four biomarkers. This potential antiinflammatory effect of CDCA on β-cells may contribute to the enhanced viability and functionality observed or be the result of such enhancement, especially when formulation stability was also optimised and physico-chemical compatibility maintained.
It appears that the bile acid Chenodeoxycholic Acid(CDCA) exerted multiple beneficial effects on the microencapsulation of NIT-1 β-cells, both from a formulation stabilisation attribute as well as biochemical and biological effects. This is illustrated which summarises the key findings of the present study. This is the is the first of its kind investigating the effect of the primary bile acid, chenodeoxycholic acid on β-cell microencapsulation. Intriguingly, various studies in our laboratory have demonstrated different effects of different bile acids on cell functions. Clearly, every bile acid exerts different impacts on microencapsulated β-cell survival and activity and some of these effects may be formulation dependent.
The incorporation of 4 % Chenodeoxycholic Acid into a formulation of 1 % SA and 0.1 % PLO used to microencapsulate NIT-1 β cells resulted in better cell viability and functionality with enhanced metabolism and bioenergetics culminating in greater insulin secretion with reduced inflammatory response. The bile acid Chenodeoxycholic Acid might be considered in the future design of appropriate biomaterial formulation systems used to encapsulate and transplant pancreatic islets and β-cells. All above were using the primary bile acid, chenodeoxycholic acid, on pancreatic β-cells in microcapsules produced using 0.8 mL/min polymer flow rate accompanied by 0.6 mL/min media flow rate.