Abstract:

Traditionally, two-dimensional (2D) adherent culture conditions have been used as a standard technique for in vitro expansion of mesenchymal stem cells (MSCs) , but their limitations are also obvious, such as the absence of tissue-specific structures, biological behavior and cellular interactions in the two-dimensional environment. In contrast, 3D cell culture is regarded as a mode simulating the growth environment in vivo. By aggregating cells into 3D spheres or attaching, extending, and growing on three-dimensional structural vectors whose components are similar to solid tissue, cell proliferation and differentiation are regulated in both time- and space-dependent manners. Thus, the characteristics and functions of cells cultured in 3D can be better preserved. The 3D spheroid culture enhances cell-cell and cell-extracellular matrix (ECM) interactions and closely mimics the natural microenvironment of a tissue as compared with traditional 2D monolayer culture. In addition, 3D culture also solves the problem of decreased proliferation of MSCs in vitro, and the capabilities of adipogenesis, osteogenesis and chondrogenesis of MSC spheroids were significantly enhanced in 3D culture. In conclusion, the preparation of MSCs spheroids (microsphere adhesion culture) is considered as one of the optimal ways to improve MSCs-based cell therapy. The application of 3D MSCs spheroids can enhance anti-inflammatory effect, promote angiogenesis, increase tissue regeneration and repair, and improve the survival rate of MSCs after transplantation. In this review, we discuss the biological characteristics and applications of MSCs spheroids under three-dimensional culture.

Key words: Mesenchymal stem cells, Three-dimensional culture, Angiogenesis, Tissue repair, Bone tissue regeneration