Health,Stem Cells, and Technology

Friday, September 23, 2011

Stem Cells Relieve Asthma

Asthma is an inflammatory disease of the airways affecting 16 million people in the United States alone and more than 300 million worldwide . In asthma, the lungs are invaded by a variety of inflammatory cells, including eosinophils and lymphocytes. These cells, in addition to mast cells that are resident in the lungs, secrete cytokines and chemokines that elicit constriction of the bronchi and secretion of mucus.

The current model for asthma suggests an abnormal shift in the Th1/Th2 balance in favor of Th2 cells and the production of IL-4, IL-5, and IL-13. Through these mediators, Th2 lymphocytes are thought to recruit additional effector cells to the lungs, and the cells recruited promote allergic inflammatory events. MSCs (mesenchymal stem cells) have been shown to have useful effects in a number of diseases and disease models. In the majority of these disorders, however, the T cell balance is shifted toward Th1 dominance. MSCs seem to modulate the immune responses and reestablish the physiological balance in a variety of autoimmune and infectious diseases and also have been able to tip the balance back to normal in an allergic environment exemplified by Th2 dominance.

Previous studies using luciferase-expressing or Q-dot–labeled MSCs demonstrated that lungs are the primary site of MSC accumulation following i.v. injection, confirming the known phenomenon of cell trapping in the pulmonary microvasculature that is partially related to cell size. Further, using Q-dot–labeled MSCs studies found significantly more MSCs retained in the lungs when rag weed-induced allergic inflammation was present compared with the unchallenged state  The primary site of pathologic processes is the lung itself, and the enhanced presence of MSCs could deliver a concentrated effort to modulate pathological immune responses.

IL-10 and TGF-β, two well characterized antiinflammatory cytokines, and IFN-γ, a key Th1 cytokine capable of down-regulating Th2-mediated pathological responses, are all thought to be capable of suppressing asthma. As IL-10 has been shown to play a significant role in the beneficial effect of MSCs in sepsis, we first measured cytokines in serum and BAL (Bronchoalveolar lavage) in the treated versus untreated RW-challenged mice. Studies find no change in IL-10 or IFN-γ levels, but there was a significant increase in the level of TGF-β, suggesting a different mechanism of action than what was found in a septic environment. We then demonstrated the importance of TGF-β in vivo by treating the mice with TGF-β–specific neutralizing antibodies before MSC injection. Blocking TGF-β—but not IL-10—eliminated the beneficial effect of BMSC treatment. A possible source of TGF-β has been shown to be the MSCs themselves, which has previously been implicated as one of the possible mediators of the MSCs’ immunosuppressive effect.

Data further suggest that IL-4 and/or IL-13 bind to IL-4R receptors on MSCs activating the STAT6 pathway. This, in turn, drives the cells to produce increased amounts of TGF-β. When this TGF-β is released from the MSCs in the allergic (i.e., Th2-dominant) environment, TGF-β receptor activation on immune cells could result in a decrease in IL-4 production and ultimately leads to a shift back toward immunological equilibrium. Surprisingly, neither recombinant IL-4 nor IL-13 alone or in combination was able to elicit the elevation of TGF-β by MSCs seen with RW-conditioned BAL fluid or blood serum in vitro. This indicates that activation of the IL-4R/STAT6 pathway is necessary but not sufficient to cause TGF-β up-regulation in MSCs. In addition to IL-4 or IL-13, there must be other important factors in vivo (present in BAL fluid or serum) that contribute to the production and subsequent release of TGF-β by MSCs.

Neutrinos Reported By CERN To Travel Faster Than Speed Of Light

Following is the official press release from CERN regarding the experimental observation that neutrinos travel faster than the speed of light. If these data are verified and replicated, this will rewrite many of the fundamental laws of physics.

OPERA experiment reports anomaly in flight time of neutrinos from CERN to Gran Sasso

Geneva, 23 September 2011. The OPERA1 experiment, which observes a neutrino beam from CERN2 730 km away at Italy’s INFN Gran Sasso Laboratory, will present new results in a seminar at CERN this afternoon at 16:00 CEST. The seminar will be webcast at Journalists wishing to ask questions may do so via twitter using the hash tag #nuquestions, or via the usual CERN press office channels.
The OPERA result is based on the observation of over 15000 neutrino events measured at Gran Sasso, and appears to indicate that the neutrinos travel at a velocity 20 parts per million above the speed of light, nature’s cosmic speed limit. Given the potential far-reaching consequences of such a result, independent measurements are needed before the effect can either be refuted or firmly established. This is why the OPERA collaboration has decided to open the result to broader scrutiny. The collaboration’s result is available on the preprint server
The OPERA measurement is at odds with well-established laws of nature, though science frequently progresses by overthrowing the established paradigms. For this reason, many searches have been made for deviations from Einstein’s theory of relativity, so far not finding any such evidence. The strong constraints arising from these observations makes an interpretation of the OPERA measurement in terms of modification of Einstein’s theory unlikely, and give further strong reason to seek new independent measurements.
“This result comes as a complete surprise,” said OPERA spokesperson, Antonio Ereditato of the University of Bern. “After many months of studies and cross checks we have not found any instrumental effect that could explain the result of the measurement. While OPERA researchers will continue their studies, we are also looking forward to independent measurements to fully assess the nature of this observation.” 
 “When an experiment finds an apparently unbelievable result and can find no artefact of the measurement to account for it, it’s normal procedure to invite broader scrutiny, and this is exactly what the OPERA collaboration is doing, it’s good scientific practice,” said CERN Research Director Sergio Bertolucci. “If this measurement is confirmed, it might change our view of physics, but we need to be sure that there are no other, more mundane, explanations. That will require independent measurements.”
In order to perform this study, the OPERA Collaboration teamed up with experts in metrology from CERN and other institutions to perform a series of high precision measurements of the distance between the source and the detector, and of the neutrinos’ time of flight. The distance between the origin of the neutrino beam and OPERA was measured with an uncertainty of 20 cm over the 730 km travel path. The neutrinos’ time of flight was determined with an accuracy of less than 10 nanoseconds by using sophisticated instruments including advanced GPS systems and atomic clocks. The time response of all elements of the CNGS beam line and of the OPERA detector has also been measured with great precision.
"We have established synchronization between CERN and Gran Sasso that gives us nanosecond accuracy, and we’ve measured the distance between the two sites to 20 centimetres,” said Dario Autiero, the CNRS researcher who will give this afternoon’s seminar. “Although our measurements have low systematic uncertainty and high statistical accuracy, and we place great confidence in our results, we’re looking forward to comparing them with those from other experiments."
“The potential impact on science is too large to draw immediate conclusions or attempt physics interpretations. My first reaction is that the neutrino is still surprising us with its mysteries. said Ereditato. “Today’s seminar is intended to invite scrutiny from the broader particle physics community.”
The OPERA experiment was inaugurated in 2006, with the main goal of studying the rare transformation (oscillation) of muon neutrinos into tau neutrinos. One first such event was observed in 2010, proving the unique ability of the experiment in the detection of the elusive signal of tau neutrinos.