I really like Paul Tesar’s idea of a “pluripotency score”, because it’s just this kind of multi-factorial definition we’ll need to really nail down just exactly what pluripotency is.
There’s a long-standing problem with trying to follow the literature on MSCs. The more proper name is “multipotent stromal cells“, whereas the name many people still use is “mesenchymal stem cells”. There’s also plenty of literature, on what is presumably the same cells, that uses “marrow stromal cells”.
To try to get around this problem in the past, I used the MeSH Browser to find the preferred term for relevant categories, searched on that, and created a feed from those results. That quit working about a month ago. According to the RSS feed for “Multipotent Stem Cells”[mh] OR “Adult Stem Cells”[mh] OR “Mesenchymal Stem Cells”[mh], nothing is new since the first week of November. I see today there’s an announcement from Pubmed about their update to MeSH for 2008, so I’m guessing there may be some connection between the two.
In the new hierarchy, multipotent stem cell, mesenchymal stem cell, and adult stem cell are all under stem cell as distinct categories. Multipotent stem cell is defined as “specialized stem cells that are committed to give rise to cells that have a particular function” whereas mesenchymal stem cell is defined as “Cells that can develop into distinct mesenchymal tissue” and Adult stem cell is defined as “Cells with high proliferative and self renewal capacities derived from adults.” I don’t know how they derived these categories, but clearly they aren’t non-overlapping categories.
Here’s what I get when I run various queries:
|mesenchymal stem cell||2180||3386|
|multipotent stem cell||708||857|
|Adult stem cell||261||642|
|all 3 with AND||3||6|
|all 3 with OR||3025||4671|
|difference of OR and summed individual results:||124||214|
So both MeSH and keyword queries lose some results when combined, and though MeSH queries lose less, they lose less of a smaller set that doesn’t contain as up-to-date results. I guess I’ll have to subscribe to each feed separately, or maybe mash them together with Yahoo Pipes or something.
Even active scientists often make mistakes when they comment on fields outside their expertise. In a recent example not involving a crackpot theory of quantum consciousness or intelligent design, Charles Krauthammer, an columnist for the Washington Post with a background in psychiatry, writes: Continue reading
Genostem is a consortium of 160 European scientists from 11 EC member countries comprising 11 academic institutions and 5 private enterprises. The project, founded in 2004, is focused on developing and applying advances in cell based therapies for the regeneration of connective tissue. However, judging from the research reported in the recent meeting, they remain competitive.
We had some interesting discussion within our group, so I thought I would share some brief thoughts.
Is stemness an artifact of tissue culture?
The first speaker was was Laure Coulombel from INSERM France. Her introductory talk was titled: “Stem cells: a single word for multiple entities”. The hypothesis presented here was that potency, as the term is usually used in the context of stem cells, is a fluid state. It’s a little like a ball on a hill, being pushed in many downhill directions at once. It only stays perched on top of the hill if the vector sum of all the forces cancel out. Apoptosis, bone differentiation, and fat differentiation all represent possible lower potential energy states but are mutually exclusive. Later on in the talk, Rocky Tuan from the NIH presented some data that seems to support this. Tuan’s experiments went like this: They transduced MSCs with the osteocalcin promoter fused to GFP. This would cause the cells to produce GFP under conditions where the OC promoter is active, which is in the late stage of osteoblast differentiation. Then they cultured cells under conditions where the cells undergo osteogenesis in vitro and the GFP increased orders of magnitude. Next, they sorted out the green cells cells by FACS, cultured them under non-inducing conditions, then switched them to fat-inducing conditions. GFP levels dropped near zero and the cells differentiated into adipocytes. After doing this, they repeated the whole thing backwards, using a PPARγ-GFP construct and going from fat to bone.
Kinda puts Yamanaka and Thomson’s work in a new light, doesn’t it?
Other items of note:
- Pierre Charbord, the Director of Genostem, presented some information about CD200, an immunoregulatory protein which is only found on the surface of undifferentiated MSCs.
- Rocky Tuan also presented his tissue engineering work on chondrocyte constructs. poly-ε-caprolactone is electrospun into a scaffold with fibers about half a cell width wide. MSCs are seeded on these scaffolds and cultured in a rotating wall culture vessel, where they grow into chondrocyte constructs the size of a tomato(~5 cm). They’re still using 8 mm punch biopsies in their cartilage repair model, however, so it could be that a significant portion of the construct is inert or merely structural; However, he did say that the scaffolding material is absorbed and replaced with proteoglycan as the construct develops.
- Katerina LeBlanc presented her work on MSCs immunomodulation in graft vs. host disease. She cautions that in some cases MSCs express MHC Class I and II and therefore can act as antigen-presenting cells in some cases, depending on the amount of IFNγ present. She also reports that MSCs produce a humoral response when cultured in medium containing FBS, but is able to reduce this by short-term culture of the cells in medium where the FBS is replaced with a small amount of the patient’s serum using a protocol our lab developed1, 2.
Apparently they have also found (and don’t ask me how, I don’t think I want to know) that MSCs are killed by HIV infection, but are resistant to EBV.
I’m pleased to see such active and interesting work being done by the new organization. One thing that is particularly striking about Genostem is the collaborative nature of the member labs. All 30 labs share the €18 million in research funding, so instead of competing with one another, they’ve joined forces and seem to be making particularly good use of what would be considered a paltry sum for an American consortium of that size.
Is it open science?
There’s no blog, and I can’t find anything on a Connotea, but Mayetic Village, a Parisian “collaborative workspace” company lists them among its customers. Unfortunately, it’s closed to nonmembers.
I’d be happy to add anyone to the MSC Biology group on Connotea, I made, but there doesn’t appear to be a way to add anyone to it once it’s been created.
I was going through my logs banning spammers (using the Antileech plug-in, so let me know if you see feed weirdness) and I was pleased to find that according to cureparalysisnow.org, I’m an excellent resource.
I don’t know much about this organization, but a cursory Google search turns up mostly other spinal cord injury and paralysis advocacy groups, so it doesn’t seem like a bad group to be associated with. Please do let me know in the comments if you have any news regarding them.
CIRM is a state-run institution with a mission to advance research in regenerative medicine, and it will be interesting to see how effective this kind of monolithic non-university institute can be in terms of making real scientific progress. The position of director is a difficult one because of the two-headed leadership approach, where the director and the advisory board chairman share the leadership role, but also because of the tremendously bright spotlight under which the chairman must labor. It’s good to see, then, that Trounson seems to know what he’s getting himself into.
Items of note from the interview are:
He says his primary mission is to push for clinical applications, but later notes that companies have been a little too short-sighted looking for instant cures. This is great because not only does it mean that he’s going to be very interested in MSCs for their ongoing clinical trials, but it also means that the institute won’t be rushing headlong into things without considering the risks. I’ve been saying for some time that more research on immune system interactions is needed, and I’m glad that people in high places are saying that too.
When asked about what he’s learned from working in reproductive medicine in Australia, he says the main thing he learned is , “Be very, very, careful what you say.”
Link to Nature article.