Spheroids from Epithelial and Mesenchymal Cell Phenotypes as Building Blocks in Bioprinting (Review)

Most tissues and organs are based on cells of the epithelial and mesenchymal phenotypes. Epithelial cells build protective barriers, have a key role in absorption and secretion, and participate in metabolism. Characterized by high plasticity and ability to migrate, mesenchymal cells ensure structural support, promote tissue restoration and are important for matrix remodeling. Interaction between these two cell types is critical for maintaining the body integrity and functioning. Modern tissue engineering is aimed at creation of artificial tissues and organs that have the required cellular composition, mechanical properties and functional potential for medical usage. One of the most popular methods of tissue engineering is 3D bioprinting, which allows creating complex three-dimensional structures with specified characteristics. Recently, special attention has been paid to bioprinting with spheroids being three-dimensional cellular aggregates that can be used as building blocks for tissue-engineered structures. Due to numerous cell-to-cell contacts and accumulation of extracellular matrix, spheroids ensure conditions allowing to form anatomical tissues and organs. To optimize bioprinting conditions, one shall precisely understand the mechanical properties of spheroids, as they directly affect the ability of cells to migrate and fuse, and thus the rate of construct formation and its overall morphology. This review summarizes the available data on the differences in mechanical properties of epithelial and mesenchymal spheroids, examines methods for their co-culturing in various applications of regenerative medicine, as well as analyzes the peculiarities of their use in different bioprinting methods to obtain high-quality tissue constructs.