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.
Where y’at? That Tuan experiment is definitely something to think about. You don’t have to go far to find people who believe that an organism is nothing more of the downstream progeny of progenitor cells. Kind of like a network of blossoming flowers. It just doesn’t make much sense does it?
Well, we are all downstream of the embryo, so there definitely a lineage, but as you know, the niches are defined by morphogen gradients, the effects of which in monolayer culture are hard to determine.