Epithelial-mesenchymal interactions drive embryonic fusion events during development and upon perturbation can result in birth defects. Cleft palate and neural tube defects can result from genetic defects or environmental exposures during development, yet very little is known about the effect of chemical exposures on fusion defects in humans because of the lack of relevant and robust human in vitro assays of developmental fusion behavior. Given the etiology and prevalence of cleft palate and the relatively simple architecture and composition of the embryonic palate, we sought to develop a three-dimensional culture system that could be used to study fusion behavior in vitro using human cells. We engineered human Wharton’s Jelly stromal cell (HWJSC) spheroids of defined size and established that 7 days of culture in osteogenesis differentiation medium was sufficient to promote an osteogenic phenotype consistent with embryonic palatal mesenchyme. HWJSC spheroids supported the attachment of human epidermal keratinocyte progenitor cells on the outer spheroid surface likely through deposition of collagens I and IV, fibronectin, and laminin, and co-cultured spheroids exhibited fusion behavior that was dependent on epidermal growth factor signaling and fibroblast growth factor signaling in agreement with palate fusion literature. The method described here may broadly apply to the generation of three-dimensional epithelial-mesenchymal co-cultures to study developmental fusion events in a format that is amenable to predictive toxicology applications.

This dataset is associated with the following publication: Belair, D., C. Wolf, C. Wood, H. Ren, R. Grindstaff, W. Padgett, A. Swank, D. MacMillan, A. Fisher, W. Winnik, and B. Abbott. Engineering human cell spheroids to model embryonic tissue fusion in vitro.. PLoS ONE. Public Library of Science, San Francisco, CA, USA, N/A, (2017).