Therapy using progenitor cells is thought to be of great interest in the future for a variety of diseases including immune-mediated diseases.
Bone marrow stromal cells (mesenchymal stem cells) are thought to “sense” their immune milieu and respond to restore balance. Wow. As the authors of a new article in PNAS comment, “is it possible to imagine a drug doing this?” Nemeth et al. (PNAS 2010 107 (12) 5652-5657; published ahead of print March 15, 2010, doi:10.1073/pnas.0910720107) present results adding to evidence that BMSCs act homeostatically regardless of the direction of immune imbalance.
Nemeth et al. begin with the known inflammation-suppressive effect of BMSC in graft/host disease in humans. This effect is thought to go in the direction of balancing Th1 inflammation toward Th2. The authors decided to look at the effects of BMSCs in a mouse model of allergic asthma to see if BMSCs could re-equilibrate aTh2 environment toward Th1/Th2 balance.
They tested this idea in mice with ragweed-induced asthma, administering syngeneic BMSCs intravenously at the time of challenge. There was virtually global suppression of all asthma-related Th2 inflammatory changes, including a decrease in serum IgE and IgG. Furthermore, the authors demonstrate that BMSCs were recruited specifically to the lung in the mice with asthma.
Looking for possible mechanisms, Nemeth et al. find that up-regulated TGF-β expression by the BMSCs is largely responsible for the anti-inflammatory effects and that this is IL-4R/STAT-6 dependent. The increased TGF-β also positively impacts T-reg numbers in the lung tissue.
Nemeth et al. note that during testing to compare BMSC response from allogeneic and syngeneic sources, they used syngeneic fibroblasts as a control and discover that the fibroblasts had beneficial effects, though the effects were milder.
Is this study going to change the paradigm for the understanding of the treatment of asthma or will it be another experimental study which has little effect in humans with asthma?
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