Abstract
Owing to the importance of stem cell culture systems in clinical applications, researchers have extensively studied them to optimize the culture conditions and increase efficiency of cell culture. A spheroid culture system provides a similar physicochemical environment in vivo by facilitating cell–cell and cell–matrix interaction to overcome the limitations of traditional monolayer cell culture. In suspension culture, aggregates of adjacent cells form a spheroid shape having wide utility in tumor and cancer research, therapeutic transplantation, drug screening, and clinical study, as well as organic culture. There are various spheroid culture methods such as hanging drop, gel embedding, magnetic levitation, and spinner culture. Lately, efforts are being made to apply the spheroid culture system to the study of drug delivery platforms and co-cultures, and to regulate differentiation and pluripotency. To study spheroid cell culture, various kinds of biomaterials are used as building forms of hydrogel, film, particle, and bead, depending upon the requirement. However, spheroid cell culture system has limitations such as hypoxia and necrosis in the spheroid core. In addition, studies should focus on methods to dissociate cells from spheroid into single cells.
Highlights
Stem cells are valuable resources in regenerative medicine with clinical and research applications (Table 1)
Human mesenchymal stem cells have secretory properties constituted by anti-inflammation, angiogenesis, and immune reaction regulation factors [1,2]
Conditions of the cell culture are very essential to facilitate the properties of stemness, maintenance, and proliferation
Summary
Stem cells are valuable resources in regenerative medicine with clinical and research applications (Table 1). Traditional two-dimension cell culture systems, wherein the cells grow as a monolayer, face some limitations in the realization of in vivo multi-cellular conditions [8]. When stem cells grow in two-dimensional cultures, maintenance of the differentiation potential and stemness is relatively more difficult than in stem cells growing in actual multi-cellular conditions [6]. Three-dimensional cell culture systems can reconstitute conditions similar to that in an in vivo microenvironment (Table 2). Mesenchymal stem cells of spheroids maintain their intrinsic phenotypic properties by cell–extracellular matrix interactions (Table 2) [11]. Spheroid stem cells regulated by hypoxia-induced upregulation of gene expression have properties of apoptosis resistance, improved viability, and secretion of angiogenic factors and chemokines (Table 2) [12,13]. Have diffusion gradient with increased spheroid size and lack of nutrients in the core of spheroid
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