They grow apart somewhat with time not because of any bad blood or inherent differences but because Isabelle comes into her own as a grown woman and doesn't need to rely on Cy as heavily as she used to, but they remain good friends until Cy dies. I've always imagined they're the kind of friends where no matter how long it's been Isabelle is always welcome to call him and it will be like no time passed at all.

As for Isabelle's future, while I'm not sure she would ever get married and I haven't definitively built that far ahead for her in this AU, she has plenty of romantic relationships other than Cy—more romantic, probably, since those two were never in love with each other. I could see her settling down with a woman sometime in her thirties or forties.