Supercharge 3D in vitro models with spheroid co-cultures

Multi-cell type spheroids recapitulate complex microenvironments

So, you are considering 3D spheroid culture as an alternative or complement to the reductionist in vitro models offered by 2D monolayer cell culture. How can you exploit 3D spheroid culture to develop a powerful experimental tool to answer your research questions?

The ability to recreate the complex microenvironments found in living tissues is the key to obtaining physiologically relevant data. Having the right cell populations in the spheroids is essential in this regard because cells secrete chemokines, growth factors, signaling proteins, and extracellular matrices that are important to supporting an environment conducive to realistic cellular interactions, responses, and behaviors.

Carefully designed 3D spheroid co-culture models will allow you to recreate the complex cellular microenvironments that are otherwise impossible with conventional approaches, enabling you to tackle your research questions and obtain life-like results.

3D spheroid co-cultures can be carried out easily and simply using 3D Biomatrix’s Perfecta3D™ Hanging Drop Plates as these plates are designed to allow convenient liquid handling and microscopic observation. We have already demonstrated several methods to create and pattern co-culture spheroids by varying the timing and order of seeding different cell types. Make sure you take a look at this data!

Here we provide a few examples that may be inspirational to you as you design your own spheroid co-culture models.

Mimicking the Tumor Niche. The niche microenvironment in which cancer cells reside plays a prominent role in the growth of cancer. By co-culturing prostate cancer cells with endothelial cells and pre-osteoblasts in 3D spheroids, the in vivo growth behavoir of malignant cancer cells within the bone metastatic prostate cancer niche can be accurately reproduced. Specifically, such a 3D co-culture spheroid model can decrease the proliferation rate of prostate cancer cells by 9 times compared to 2D monolayer culture, producing results in good agreement with in vivo experiments.

Monitoring 3D Migration of Cells. Cell migration and tissue invasion is an important issue in tumor and developmental research. By confronting spheroids formed by one fluorescently labeled cell population with another fluorescently labeled cell population, cell invasion can be easily followed microscopically. Chemokines and chemotactic growth factors can be used to monitor chemotaxis and cell migration in 3D.

Engineering Tumor Models. Single cell type spheroids do not model the stromal-epithelial interactions that have an important role in controlling tumor growth and development in vivo. By adding epithelial cells to pre-formed fibroblast spheroids, realistic 3D tumor models can be formed that contain both stromal and malignant epithelial cells with an architecture that closely resembles that of tumor microlesions in vivo. A variety of cancer types has already been demonstrated, such as breast, prostate, colon, pancreas and urinary bladder. These tumor models can be used to screen pharmaceutical agents, as reference specimens, and to study tumor development and progression.

Sources:
Prostate Cancer Co-Culture Spheroids http://www.sciencedirect.com/science/article/pii/S0142961209002294
Spheroids Confrontation Assay http://www.sciencedirect.com/science/article/pii/S0940960211000355
Tissue Engineered Tumor Models http://informahealthcare.com/doi/abs/10.3109/10520295.2010.483655