(verbatim) Use of alginates to encapsulate cells in order to provide mechanical support and immunoprotection is common practice in the development of a bioartificial pancreas. Alginate is a family of linear binary heteropolymers composed of a-L-guluronic acid and b-D-mannuronic acid residues in various proportion, sequence, and molecular weight. Given their variety in composition, it is our hypothesis that the behavior of encapsulated cells will depend on the composition of the alginate matrix. It is our objective to study the interaction between alginate matrix and encapsulated cells in model tissue-engineered pancreatic constructs. These model constructs are composed of neonatal porcine islets or mouse insulinoma bTC3 cells encapsulated in one of four different types of alginate.
The specific aims of the proposed research are to determine the property of alginate gel responsible for affecting the behavior of encapsulated cells, and conversely to investigate the affect of encapsulated cells on the alginate matrix, in vitro and in vivo. To complete the first specific aim, the metabolic and secretory profiles of the encapsulated cells will be monitored, and the apoptotic, proliferative, viable and necrotic cell fractions determined. To complete the second specific aim, 1H NMR techniques will be employed to monitor changes in the alginate matrix. Overall, the proposed experiments are a thorough investigation of the interaction between alginate, as an extracellular matrix, and encapsulated cells. The criteria to judge this interaction are: insulin secretion; bead integrity; cell growth; and in vivo stability. It is anticipated that we will identify alginate compositions that are beneficial to a tissue-engineered pancreas as well as compositions that are inappropriate. Furthermore, the proposed NMR experiments will enhance our understanding of the capabilities of NMR to monitor a tissue-engineered construct in vitro and in vivo.
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| Black, Sasha P; Constantinidis, Ioannis; Cui, Hong et al. (2006) Immune responses to an encapsulated allogeneic islet beta-cell line in diabetic NOD mice. Biochem Biophys Res Commun 340:236-43 |
| Simpson, Nicholas E; Khokhlova, Nata; Oca-Cossio, Jose A et al. (2005) Effects of growth regulation on conditionally-transformed alginate-entrapped insulin secreting cell lines in vitro. Biomaterials 26:4633-41 |
