Hugo Alves from Twente University in the Netherlands gave an interesting talk during the ISSCR on the role of DNA damage, senescence and differentiation of bone marrow derived Mesenchymal Stem Cells (MSCs). At first I thought it was obvious that senescent cells would lose their ability to differentiate into the canonical three differentiation endpoints of MSCs, but then it got me thinking. The DNA damage that Dr. Alves was observing as the cells went through multiple population doublings was most likely due to telemere crisis, as hTERT immortalized MSCs, which do not senesce, maintained their ability to differentiate. In fact, many groups have used this sacrilegious cell line, including a paper a really enjoyed from Tom Misteli’s group.
This makes me wonder about the extent to which MSCs can be expanded ex vivo. It is already known that MSCs are a heterogeneous population of cells, and that if you even look at them wrong they lose their magical power and become totally fibroblastic and useless. The transcriptome of MSCs can differ as much within donors of a different passage as between different donors of the same passage. Labs routinely use MSCs at very low passages so as to ‘keep ‘em fresh’. They fear about trypsin chomping away at the surface proteins. They lose sleep over the concentration of FBS in their media, and the degree to which the plastic is evenly tissue culture treated. I’ve even seen a man killed because he stacked too many plates which could mess up the temperature distribution in the incubator. What I’m trying to say is that the folklore surrounding how one cultures MSCs is the equivalent to an old lady sitting by a slot machine who has to rub her lucky teddy bear three times and rotate on her stool while praising Jesus in an obsessive manner before she pulls the lever. They’ve amassed a skill set that they think will land them the right cells, but still can’t be guaranteed of it.
Precautions like those mentioned above make me vomit a little in my mouth every time I read a paper utilizing the hTERT MSCs. But at the end of the day, this messed-up cell line maintains its ability to differentiate, while pampered, super-classified MSCs can flat-out suck. Of course, that’s not to say that differentiation is the only thing that defines an MSC. For example, the subjective opinion on how ‘good’ the cells look, as well as obvious things like genomic integrity are also weighed heavily in the decision.
It would be great if something a little more reliable than X-Gal staining could give you information on the degree of senescence in your culture, maybe there is. . . I dunno . . . sleepy.
The Niche has a great write-up on the iPS panel during the ISSCR
Well, I’m home. Time to sit back and think about what I can remember about what was certainly an informative conference. Click the more button to read some summaries of some of the talks. I’ll keep adding to this as my motivation piques. 
One of the challenges of living in the US that I’ve had to deal with is an onslaught of morons who think that I come from a backwards liberal nightmare-land where everyone is uneducated and has no access to high standard health care. I explain slowly that they are slightly misinformed, despite the fact the Canadian system of health care definitely has some drawbacks. But then they tell me about their friend, Steve, who they knew once who broke his leg and couldn’t get adequate medical attention so now he has Parkinsons or something along those lines. The anecdote of Steve is therefore the defining proof that all in Canada is horribly aloof.