Tuesday, 16 October 2012

Stem cells :Running before we can walk?

Payne NL, Sun G, McDonald C, Layton D, Moussa L, Emerson-Webber A, Veron N, Siatskas C, Herszfeld D, Price J, Bernard CC Distinct immunomodulatory and migratory mechanisms underpin the therapeutic potential of human mesenchymal stem cells in autoimmune demyelination.Cell Transplant. 2012 Oct 4. doi: 10.3727/096368912X657620. [Epub ahead of print] 

Mesenchymal Stem cells (MSCs) are efficacious in a variety of intractable diseases. Whilst bone marrow (BM) derived MSCs (BM-MSCs) have been widely investigated, MSCs from other tissue sources have also been shown to be effective in several autoimmune and inflammatory disorders. In the present study we simultaneously assessed the therapeutic efficacy of human BM-MSCs, as well as MSCs isolated from adipose tissue (Ad-MSCs) and umbilical cord Wharton's jelly (UC-MSCs), in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Prior to in vivo experiments, we characterized the phenotype and function of all three MSC types. We show that BM-MSCs were more efficient at suppressing the in vitro proliferation of mitogen or antigen-stimulated T-cell responses compared to Ad-MSCs and UC-MSCs. Notably BM-MSCs induced the differential expression of cytokines from normal and stimulated T-cells. Paradoxically, intravenous transplantation of BM-MSCs into C57BL/6 mice with chronic progressive EAE had a negligible effect on the disease course, even when multiple MSC injections were administered over a number of time points. In contrast, Ad-MSCs had the most significant impact on clinical and pathological disease outcomes in chronic progressive and relapsing-remitting EAE models. In vivo tracking studies revealed that Ad-MSCs were able to migrate to the central nervous system (CNS), a property that most likely correlated with their broader expression of homing molecules, while BM-MSCs were not detected in this anatomic region. Collectively, this comparative investigation demonstrates that transplanted Ad-MSCs play a significant role in tissue repair processes by virtue of their ability to suppress inflammation coupled with their enhanced ability to home to the injured CNS. Given the access and relatively ease for harvesting adipose tissue, these data further implicate Ad-MSCs as a cell therapeutic that may be used to treat MS patients.


There is immense interest in the application of stem cell technology. The hype is that we can regenerate nerves and repair damage but the current reality is not so upbeat. Because of the clamour to research stem cells there are trials of mesenchymal stems cells already, but if we look at the studies from animals have they show they they can make new oligodendrocytes and nerves which is what we want stem cells to do. Well maybe a bit but they seem to modulate the immune reaction more...something we can go better with immune modulation drugs already. This study they looked at the effect of bone marrow-derived stem cells, umbilical cord stem cells and stem cells from fat (adipose tissue) after they were put in mice with MS-like disease. Mesenchymal stem cells did not do anything but fat derived stem cells did something..although not sure if it was making myelin and nerves. This study suggests that fat-derived stem cells are more interesting than mesenchymal stem cells, but the latter are in trial already. 

This is because of the public pressure to get stuff moving, but are we moving too fast as we do not want to kill the approach before it has got off the ground. This is a concern

2 comments:

  1. Do you think we're moving too fast? When will be a better time?

    144 years in the making and there's zilch for progressive MS. Everything I've read suggests that stem cells will deliver the only real promise in terms of stopping and repairing damage.

    While I agree with you that Neil Scholding's work at Bristol seems premature and lacking convincing evidence, we really do need to invest more brain power and money into stem cell research. It's our only real hope.

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    Replies
    1. Yes I agree but if you look at gene therapy, which was the last great hope, they put a viral gene therapy thing into a guy and killed him.
      sort of killed off that line of work a few minutes thought and that effect was predictable

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