Alginate matrices to regulate granulosa cell morphology and steroid production

The ability to mature granulosa cell-oocyte complexes (GOCs) in vitro may provide a mechanism to preserve the reproductive potential of women. Systems to mature GOCs in vitro must maintain the granulosa cell (GC)-oocyte interactions and coordinate the development of the oocyte. We propose that alginate based hydrogels can function as a synthetic stroma that maintains the three-dimensional architecture of the GOC. Additionally, the scaffold can regulate GC interaction with the extracellular matrix (ECM), which has been shown to affect differentiation, proliferation, and steroid production. Alginate was modified with minimal peptide sequences from ECM proteins. GCs attach and spread on peptide-modified surfaces, but not unmodified surfaces, and maintain proliferation rate. Progesterone production, an indicator of granulosa cell differentiation, increased up to a 3 fold on RGD modified alginate. These results indicate that the scaffolds can regulate GC differentiation, which will be a component of three-dimensional alginate scaffolds for in vitro maturation of GOCs. Additionally, this system provides an in vitro model to examine the role of cell-cell and cell-ECM interactions in tissue development.