I believe the maximum number of domains supported per Multi-Domain Server is 250.
If you are doing an HA/Load Sharing configuration, the group of MDS total can managed 250 domains.
VSX itself only supports up to 250 VS per cluster also.
The only way you're getting to 500 of either is multiple VSX clusters and multiple MDS clusters.
In any case, the individual VSes of a VSX gateway/cluster can be managed by the same group of Multi-Domain Servers, with different VSes being managed by different domains.
I don't believe the same VSX gateway/cluster can be managed by different groups of MDS servers.