Intrinsic cellular properties of several types of cells are dramatically altered as
the culture condition shifts from two-dimensional (2D) to three-dimensional (3D) environment.
Currently, several lines of evidence have demonstrated the therapeutic potential of
mesenchymal stem cells (MSCs) in regenerative medicine. MSCs not only replenish the
lost cells, they also promote the regeneration of impaired tissues by modulating the
immune responses. Following the development of 3D cell culture, the enhanced therapeutic
efficacy of spheroid-forming MSCs have been identified in several animal disease models
by promoting differentiation or trophic factor secretion, as compared to planar-cultured
MSCs. Due to the complicated and multifunctional applications in the medical field,
MSCs are recently named as medicinal signaling cells. In this review, we summarize
the predominant differences of cell-environment interactions for the MSC spheroids
formed by chitosan-based substrates and other scaffold-free approaches. Furthermore,
several important physical and chemical factors affecting cell behaviors in the cell
spheroids are discussed. Currently, the understanding of MSCs spheroid interactions
is continuously expanding. Overall, this article aims to review the broad advantages
and perspectives of MSC spheroids in regenerative medicine and in future healthcare.