Aim Insulin resistance, a key factor in type 2 diabetes, has been challenging to model in vitro. This limits drug screening to in vivo models. To address this, we developed a 3D co-culture system using adipose-derived mesenchymal stem cells (ADMSCs) and macrophages with custom co-culture plates to enhance drug selectivity for humans.
Material and Methods Our 3D co-culture plates separate ADMSCs and RAW264.7 cells with hydrogels, allowing interaction via shared media. Hydrogels were created with a mix of alginate, gelatin, and type I collagen using a 3D cell-printing system. Cells were stabilized and cross-linked in CaCl2 before a 12-day culture period. Assays were conducted on separated wells of adipocytes and macrophages.
Results Compounds KR-1, KR-2, and KR-3 were tested on 3D co-cultured mouse 3T3-L1 adipocytes and human ADMSCs. Glucose uptake assays and western blot analysis showed KR-1 and KR-3 improved insulin sensitivity in 3T3-L1 adipocytes, while KR-2 was more effective in ADMSC adipocytes. These findings suggest species-specific drug effects on insulin resistance.
Conclusions Our 3D co-culture model effectively mimics insulin resistance and can be used to screen anti-obesity and anti-diabetic drugs for human and mouse cell types. This system may accelerate the development of species-specific therapies.
-Science journal cover design by scapiens
https://dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1111/dom.14033
