Dear all, I am trying to create co-culture systems using different cell types. I have realized that for some cell types, when mixed together, do not produce any aggregations or polarizations, while others do. Why does this happen and what is their biological significance? Is there anything useful which i can learn from these cell behaviours? For your responses, please.
Thank you.
Warmest regards,
Justin
The simple answer is that what you are modeling is the tissue microenvironment when co-culturing mixed populations. There are a lot of studies that have shown tremedous amount of variability (in immune responses, pathology, etc) from the same tissue depending on the microenvironment. Tuberculosis is a great example. Even in RA there is speculation that you don't have the same type of disease pathology from joint to joint. And it is definately true to cancer.
As to why it happens... well... cell populations, the numbers of each cell type, where the cell types are, who they are in contact with, and a variety of other factors can lead to changes in what cytokines/chemokines and other secreted proteins that will be produced. Not only do you have cell modulation by cell-to-cell contact, but the secreted proteins also operate on a diffusion gradient.
But given that co-culture can help with modeling the tissue microenvironment, also understand that there are limitations to this model. The in vivo microenvironment is not just made up of infiltrated cells, but also tissue specific cells, such as epithelial, endothelial, etc. and also individualistic proteins (including a lot of other stuff that we can't do in vitro, such as hormones). And these also make a impact on the response in the microenvironment. And not to mention the cell to cell contact with these cells, and operating in a 3D versus a 2D environemnt.
This phenomenon has been known for over 70 years. It was noticed in the 1950s, for example, that if you break up a living sea sponge its cells can re-form aggregates in which 'outer' and 'inner' cells sort back to original positions.
You can even mix two species of sponge, and the cells of each species will sort out:
Article The Role of Specific Surface Antigens in Cell Adhesion. Part...
The mechanistic explanation is that cell-surface adhesion molecules bind more strongly to "like" cells than to "unlike" cells. This was demonstrated to me in an undergraduate biology course 30 years ago. Our instructor had us push red and yellow sponge bits through a sieve and then digest them into single-cell suspensions, which we combined. The next day there were yellow blobs and red blobs, but none mixed.
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