Paper: Mesenchymal Stem Cell-Derived Molecules Reverse Fulminant Hepatic Failure

Returning on what I was saying last Wednesday... I was testing out Technorati and found many blogs that had just copied and pasted a stem cell news from The Press Association or from BBC News.

This is a kind of approach I don't really support and I am very disappointed by the fact that it's so common: why do these bloggers fill the Internet with duplications of news articles? No one has written a single word of comment. I guess that isn't really useful (or perhaps for the Google spiders yes...).

What I would like to do now and in the future is review interesting papers in the simplest way possible, leaving back stuff that's too geeky and adding here and there my personal opinions. I hope you will approve and enjoy this kind of approach.

First of all: here is the complete reference. I just can't stand when the journalists write: "a group of researchers for the XYZ hospital..." - everyone who is interested in going more in depth should be given the opportunity to look at the original paper!

Parekkadan B, van Poll D, Suganuma K, Carter EA, Berthiaume F, et al. (2007) Mesenchymal Stem Cell-Derived Molecules Reverse Fulminant Hepatic Failure. PLoS ONE 2/9

Human mesenchymal stem cells (MSCs) reside in the bone marrow next to the hematopoietic stem cells: they can differentiate in various cell types and have been shown to interact with the latter ones, creating a special microenvironment that regulates their growth.
This regulation is made through particular molecules that MSCs produce. Could these molecules modulate also the Fulminant Hepatic Failure (FHF)? This is what this study shows us.

No significant benefit was seen after the intravenous infusion of 2×106 human MSCs 24 hours post-induction, which is most likely due to poor engraftment, entrapment in the alveolar capillary bed and/or immune rejection of the cells

This is quite interesting but it hasn't worked, I will come back on this later.

What worked best instead was a MSC-conditioned medium which was prepared by collecting the medium after 24 hour culture of different cell masses (this means getting modulating molecules that the MSCs release in the liquid they live in culture) and an extracorporeal perfusion with a bioreactor containing MSCs

These therapies made many of the rats survive longer. Something in that MSC-conditioned medium must benefit: the paper suggests (with further histologic analysis) making leukocytes emigrate from the liver.

The authors have searched for what is actually in the medium. So what they have found is real immunomodulatory cocktail with IGFBP-1m Leptin, CLL2, IL-8, BMP-4, FasL, FGF-6, TNF-beta ad so many others.

Some personal conclusions:

- MSCs really have a great immunomodulatory role with all those cocktail ingredients

- When I read the BBC news I though of MSCs used as such, to regenerate or at least modulate in situ. This is a cocktail of what MSCs produce.

- Nonetheless this opens new perspectives on the potential biological role of MSCs and all it's molecules with the immune system. Maybe researchers could seek which molecules * in particular * where actually useful.

- I am curious to know why those human MSCs used directly as such didn't give any result. Did they actually get to the liver or crammed all in the alveolar capillaries?