Diabetes and heart failure are diseases of enormous burden to Americans, and current therapies for theseoften-lethal diseases are clearly inadequate. The generation of organs suitable for transplantation offerstremendous potential to treat these types of diseases. The early development of over 20 mammalian organsinvolves the sequential, ordered exchange of signals between interacting epithelial and mesenchymal cellpopulations, resulting in their progressive differentiation. We hypothesize that this complex, dynamicregulatory network can be resolved by the integration of different scientific disciplines and used to designand build organ precursors or parts.As a part of the larger SysCODE consortium we will develop technologies that can be used to engineer thesurrounding microenvironment. We propose to develop novel, three dimensional (3D) microscale constructsto be used as tools to study populations of interacting mesenchymal and epithelial cells . These microscaletechniques will enable the biomimecry of the complex 3D structure of epithelial and mesenchymal cellinteractions that occur in the embryonic in vivo environment. In vivo, the cellular environment is tightlyregulated in 3D by interactions between cell-cell, cell-extracellular matrix (ECM) and cell-soluble factors. Toeffectively mimic mesenchymal and epithelial tissue we will engineer novel hydrogels embedded with celltypes that resemble the cells native to these tissues. Addition features such as the basement membrane willalso be engineered to fascilitate the movement of growth factors and environmental cues between the twotypes of tissue. This will all be accomplished through the successful completion of the following threeSpecific Aims:
Aim 1 : To develop biomimetic materials for engineering the cell-ECM interactions within 3Depithelial-mesenchymal constructs.
Aim 2 : To fabricate microscale constructs that can be used to study the interactions betweenepithelial and mesenchyme cell populations.
Aim 3 : To develop and validate a combinatorial approach to study microenvironmental factors ininteracting epithelial and mesenchymal cell populations.
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