3D co-culturing model of primary pancreatic islets and hepatocytes in hybrid spheroid to overcome pancreatic cell shortage

Optimization of Albumin Secretion and Metabolic Activity of Cytochrome P450 1A1 of Human Hepatoblastoma HepG2 Cells in Multicellular Spheroids by Controlling Spheroid Size

“…Therefore, multicellular spheroids are considered useful in vitro systems for drug screening, including tests of drug metabolism and toxicity, [1][2][3][4][5][6] and for studying tumor metastasis. 7,8) Furthermore, such spheroids have attracted much attention for application in cell-based therapy [9][10][11] and as a building block for the construction of large tissues. 12,13) In a previous study, we demonstrated that spheroid formation greatly prolonged the survival of insulinsecreting NIT-1 cells after transplantation in mice.…”

“…In contrast, microfabrication is suitable for the development of sizecontrolled microwells with narrow size distribution. 10,21,22) In a previous study, we demonstrated that polydimethylsiloxane (PDMS)-based microwells constructed using a microfabrication technique could be used to obtain spheroids with a very narrow size distribution. 23) We also found that coating the microwells with poly(N-isopropylacrylamide) (PNIPAAm), a thermoresponsive polymer, increased the quality of the spheroids, since the coating prevented the cells from adhering to the PDMS-based microwells.…”

Formation of size-controllable spheroids using gingiva-derived stem cells and concave microwells: Morphology and viability tests

“…The shape of the microwell can be modified into different shapes, including rectangles and triangles (3). Various cell types have been applied to microwells, including embryonic stem cells, islet cells and hepatocytes (5,17,18). A previous study suggested that size may be an important parameter that influences cell differentiation (19).…”

“…Single primary islet cells have been co-cultured with adipose-derived stem cells in concave microwells, resulting in improved viability and function (17,18,28). Stem cells may have significant potential to protect primary cells from damage during culturing and may be employed to improve cell survival and function prior to transplantation (17).…”

“…Stem cells may have significant potential to protect primary cells from damage during culturing and may be employed to improve cell survival and function prior to transplantation (17). Another study used primary pancreatic islets and hepatocytes for the three-dimensional co-culture model, and these two types of cells appeared to strongly support the functions of each other as spheroids, even though smaller proportions of each cell type were evaluated when compared to the mono-culture models (18). Size-controllable spheroids with primary hepatocytes and hepatic stellate cells secreted more albumin compared to the mono-culture hepatospheres, and the enzymatic activity of co-cultured heterospheres was higher compared to that of a mono-culture of hepatospheres (28).…”