Analysis of cell-cell and cell-matrix interactions in three dimensional biomaterial coculture systems.

摘要

The in vivo microenvironment presents a complex milieu of multifaced cues to the cells which reside in it. These cues, based upon cell-cell interactions, cell-matrix interactions, and soluble factors, are controlled both spatially and temporally. Regulation of these signaling cues is vital for tissue development and homeostasis. As a result, when this signaling is disrupted, it can lead to developmental abnormalities or disease states, such as arthritis and tumor development. This work focuses on understanding the influence of the extracellular matrix on dictating cell and tissue interactions in normal cartilage, osteoarthritis, and mammary gland development. Current understanding of these properties is limited by the use of two dimensional culture systems. This work seeks to utilize three dimensional biomaterial culture systems to provide a more sophisticated model of the in vivo microenvironment while maintaing a precise control of the matrix properties. This is accomplished through application of poly (ethylene glycol) based systems. Results demonstrate that MSC stimulation of cartilage tissue formation is dependent on the differentiation state of the MSCs. Furthermore, in osteoarthritic chondrcytes, spatial orientation between cell populations is an important factor in the MSC stimulatory capacity. Finally, matrix rigidity and pore size was found to be permissive rather than instructive for mammary gland organoid branching with tumor organoids retaining the capacity to branch in stiffer matrixes as compared with normal tissue.