One of the simplest methods to create co-culture spheroids containing multiple cell types is to seed the different cell types together into a low attachment round bottom plate such as the Corning spheroid microplate. The cells can be seeded at the same time or added at different time points. Here is an application note as an example that uses tumor cells from a lung cancer cell line and primary human lung fibroblasts for reference. In this example, PBMCs were also included as a treatment in the wells, but were not shown to be incorporated into the spheroid. When working with multiple cell types some optimization may be required. For example, different media conditions may need to be tested and some models may require the addition of extracellular matrices such as Corning Matrigel matrix. The cells may also have different doubling rates so cell seeding densities for each cell type may need optimization as well. You can also access this guidelines for use document on considerations for 3D cell culture as another useful resource.