Abstract
Three-dimensional multicellular spheroids (MCSs) have received extensive attention in the field of biomedicine due to their ability to simulate the structure and function of tissues in vivo more accurately than traditional in vitro two-dimensional models and to simulate cell–cell and cell extracellular matrix (ECM) interactions. It has become an important in vitro three-dimensional model for tumor research, high-throughput drug screening, tissue engineering, and basic biology research. In the review, we first summarize methods for MCSs generation and their respective advantages and disadvantages and highlight the advances of hydrogel and microfluidic systems in the generation of spheroids. Then, we look at the application of MCSs in cancer research and other aspects. Finally, we discuss the development direction and prospects of MCSs
Highlights
In the 1980s, Weaver systematically summarized the relationship between cells and the extracellular matrix (ECM) and constructed a threedimensional cell culture (TDCC) model in the study of breast cancer cells, which gave birth to three-dimensional culture technology
The results showed improved proliferation, spheformation and invasion of U87 glioma cellscells transfected withwith hypoxia-inducible factors roid formation and invasion of U87 glioma transfected hypoxia-inducible fac(HIFs) compared to non-treated cells
The study found that the number of spheroids formed by co-culturing fibroblasts breast cancer cells was lower than that of breast cancer spheroids prepared alone, and when and breast cancer cells was lower than that of breast cancer spheroids prepared alone, and macrophages were added, the frequency of spheroids increased
Summary
In the field of biomedicine, cell biology is researched by culturing cells in vitro. Traditionally, cells are cultured in a petri dish or a culture bottle using a two-dimensional culture method. In the three-dimensional cell culture, cells spontaneously aggregate and form compact multicellular spheroids (MCSs) when combined with cadherin [1]. Systematic helping to build a bridge between in vivo and in vitro biology So far, a seriesreview of cells have been explored for the production of MCSs, including cancer cells [4,12], induced velopmentpluripotent and application of these methods. This a stem cells [13,14], and fibroblasts [15,16]. The loose cell aggregates form dense spheroids under the strong hemophilic interaction of epithelial cadherin
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