There are many papers about this. Here you might find hints (don't read it by myself):

http://openi.nlm.nih.gov/detailedresult.php?img=3102737_pgen.1002085.g004&req=4

http://www.ncbi.nlm.nih.gov/pubmed/22200372

http://www.google.com/search?q=long+term+cultivation+ips&sourceid=ie7&rls=com.microsoft:de:IE-SearchBox&ie=&oe=

Before 20 passages we used to consider it an early line, from 20-40 a safe window for working and after 40 you have to karyotype every 5 passages or so to confirm they are normal... Actually if you perform regular enzymatic splitting, the chances of accumulating trisomies are high as i checked myself in several instances...

With good culture techniques, they should indefinitely maintain self-renewal. I have a line that is hitting 83 passages and is still differentiating into 90% cardiomyocytes like a pro!

From my experience, I have found that differentiation potential plummets in long term culture in feeder-free conditions using MEF-conditioned medium. I have no concrete evidence for this, but I feel like it's true. If using MEF-CM, you should keep them on feeders and transfer to feeder-free for no more than 5 passages.

I feel that long-term culture in MEF-CM exerts a selection pressure on the cells, and consequently there is genetic drift. My belief is that the self-renewal pathways are down-regulated and lineage-priming occurs. It's interesting, because genetically 'drifted' cells robustly continue to express the 6 conventional pluripotency markers by ICC, yet they do not differentiate! My hypothesis is that they are coexpressing lineage-priming genes along with the pluripotency genes, which has a deliterious effect on on directed differentiation.

Again, these are my own personal beliefs so take them as that! ;-) If you choose to do long term-culture in feeder-free conditions, you are better off using a commercially available defined medium that has been optimized for this purpose (mTesR1, TeSR-E8, etc).

Best,