Three-Dimensional Spheroid Culture on Polymer-Coated Surface Potentiate Stem Cell Functions via Enhanced Cell–Extracellular Matrix Interactions

The
aggregation of mesenchymal stem cells (MSCs) into three-dimensional
(3D) spheroids has emerged as a promising therapeutic candidate for
the treatment of a variety of diseases. In spite of the numerous 3D
culture methods suggested recently for MSC spheroid generation, it
is still elusive to fully reflect real stem cell niches; this effort
majorly suffers from a lack of cell–extracellular matrix (ECM)
interactions within the 3D spheroids. In this study, we develop a
simple but versatile method for generating human MSC (hMSC) spheroids
by culturing the cells on a functional polymer film surface, poly­(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl
cyclotetra­siloxane) (pV4D4). Interestingly, the pV4D4-coated
surface allows a dynamic cell adhesion to the polymer surface while
developing the formation of 3D spheroids. The corresponding mechanotransduction
promotes the expression of the endogenous ECM and, in turn, results
in a remarkable improvement in self-renewal abilities, pro-angiogenic
potency, and multilineage differentiation capabilities. This observation
highlights the significance of our method compared to the conventional
spheroid-generating methods in terms of recreating the ECM-rich microenvironment.
We believe the developed surface can serve as a versatile but reliable
method for stem cell-based tissue engineering and regenerative medicine.