What about the mediana average of all the studied genes (in this case you need 20-30 canididates to validate).

I'm not an exosome expert, but it would make sense to use an mRNA that is abundant in the cytosol or the compartment from where the exosome originates. As with any reference, this specific mRNA should be stable under the conditions that you are testing and freely incorporated (no signaling or activation needed) into the exosomes under a variety of conditions.

We're using 5S

We routinely use U6 RNA and it is working very well. The advantage is that the human and murine U6 are identical so you can use the same housekeeping gene for murine and human studies.