Recent Advances in Three-Dimensional Multicellular Spheroid Culture and Future Development

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

TGFβ1 Secreted by Cancer-Associated Fibroblasts as an Inductor of Resistance to Photodynamic Therapy in Squamous Cell Carcinoma Cells

“…In this sense, migration assays using A431 spheroids showed that CAF-derived CM could also promote EMT, since increased explant expansion was observed from A431 spheroids treated with CAF-derived CM in combination with PDT compared to PDT alone. This results are in line with existing literature [ 44 ] and a deeper characterization of this aspect will need to be addressed in future studies. Overall, these data broaden the implications of our findings, as the use of multicellular spheroids is a powerful tool that more accurately mimics the in vivo events.…”

“…In this regard, the reduced basal ROS levels found in SCC13 cells may contribute to the intrinsic relative resistance to PDT displayed by this cell line and limit the susceptibility to develop increased resistance to PDT in response to exogenous TGFβ1. Accordingly, some authors have evidenced that higher secretion levels of endogenous TGFβ1 can reduce the sensitivity to exogenous TGFβ1, probably due to the saturation of the pathway by the autocrine signalling [ 44 , 48 , 49 ]. Hence, the high secretion levels of TGFβ1 found in SCC13 cells could further explain the lack of resistance to PDT observed in this cell line in the presence of TGFβ1.…”

“…The development of resistance to therapies in response to TGFβ1 has been tightly related by other authors to the slowing down of cell cycle progression [ 22 , 36 , 44 , 48 , 50 ]. In agreement with this, our data suggest that A431 cells undergo a decrease in proliferation upon the exposure to TGFβ1, evidenced by a shift into more flattened morphologies and the reduction in the mitotic index.…”

Engineering Biological Tissues from the Bottom-Up: Recent Advances and Future Prospects

“…-High production costs. [11,25,28,47,98,[106][107][108][109][110][111][112][113][114][115][116][117][118][119] Using acoustic assembly, only a few seconds are needed to obtain simple geometry of microgel units. In addition to this, cell viability can also be highly maintained through this method.…”

“…With the help of these unique fluid phenomena, microfluidic can achieve a series of micromachining and micromanipulation. Now, microfluidic is considered to have great development potential and wide application prospects in biomedical research [25,98,[109][110][111][112]. With respect to in vitro bionics, microfluidic chips are very suitable for realizing physiological functions at the level of tissues and organs in vitro by using biomaterials such as bionic microstructures and hydrogels, which are also called "organ-on-chips" [113][114][115].…”