An In Vitro Model System Based on Calcium- and Phosphate Ion-Induced hMSC Spheroid Mineralization

Recreating the three-dimensional microenvironment of bone in the culture dish would allow the study of musculoskeletal disorders and the creation generation of building blocks for bone regeneration. In this study, we propose the use of a microwell-based platform to create spheroidal aggregates of human mesenchymal stromal cells and apply ionic calcium and phosphate supplementation to achieve rapid mineralization.

These mineralized spheroids promote an osteogenic gene signature in cells through the influence of the spheroids biophysical environment and inorganic signaling, and require less calcium or phosphate to achieve mineralization compared to a monolayer culture. In addition, we found that mineralized spheroids represent a physiological model suitable for small molecule perturbations and the study of extracellular vesicle calcification.