Lab Notes: Enzyme Turn-On Turns Off Aspects of Aging
By MedPage Today Staff
Published: November 26, 2010
A hint at a way to reverse aging -- at least in mice -- platelets from skin cells, and a potential new therapeutic target for triple-negative breast cancer are all featured in this week's lab Notes.
Fountain of Youth for Mice?
If a mouse has cancer, there are some very good treatments ... or so the cancer researchers quip.
The same may be true if a mouse gets old, according to researchers reporting in Nature.
As mammals age, the tips of the chromosomes -- the telomeres -- get progressively shorter. And mice that are lacking an enzyme that rebuilds those tips suffer from tissue atrophy, stem-cell loss, organ failure, and impaired healing, according to Ronald DePinho, MD, of the Dana-Farber Cancer Institute in Boston, and colleagues.
But in mice that are genetically engineered so the enzyme could be turned back on, several of those effects were reversed, leading to -- among other things -- the creation of new brain cells, and an improved sense of smell.
The findings hint at strategies to reverse aging in other mammals, including those performing the experiments.
The downside is that -- as is often the case in cancer -- only the mice have benefited so far.
-- M.S.
Skins Cells Become Platelets
Japanese researchers have developed a way to create human platelets by transforming skin cells into pluripotent stem cells, which may eventually help patients with thrombocytopenia.
The team, led by Koji Eto, MD, PhD, of the University of Tokyo, first reprogrammed human skin cells into a more stem-cell-like state and then cultured them. As reported in the Journal of Experimental Medicine, cells with reduced activation of the gene c-MYC during differentiation after initial reactivation more efficiently generated platelets in vitro. c-MYC plays a role in both embryonic and adult hematopoiesis.
When the researchers injected the resulting platelets into mice with thrombocytopenia induced by irradiation, the platelets behaved like normal ones, circulating and accumulating at a site of injury.
The findings may lead to the ability to create patient-specific platelets, which would overcome the problem of immune rejection in patients with thrombocytopenia who receive donor platelets.
"We propose that induced pluripotent stem cell platelets could be an invaluable resource for patients requiring repeated platelet transfusion and that this system should enable us to investigate as yet unresolved aspects of the mechanisms underlying thrombocytopenia," Eto and his colleagues wrote in their paper.
-- T.N.
Umbilical Cord Stem Cells Target RA
Umbilical cord mesenchymal stem cells have been shown, for the first time in an animal model, to ameliorate the joint inflammation characteristic of rheumatoid arthritis.
A group of researchers from Peking University found that in mice with collagen-induced arthritis, the administration of human umbilical cord stem cells, which are capable of greater differentiation and immunomodulation than bone marrow stem cells, resulted in reductions in proinflammatory cytokines and chemokines such as tumor necrosis factor-alpha and interleukin 6.
The treatment also suppressed the activity of fibroblast-like synoviocytes, which are known to play a critical role in both the immune activation and the tissue damage seen in the arthritic joint.
Targeting these synoviocytes with stem cells, according to the researchers, might offer a new therapeutic approach for the treatment of autoimmune diseases such as rheumatoid arthritis -- without the need for any invasive procedure to harvest the cells.
-- N.W.
Pain Tx Soothes Multiple Sclerosis
An experimental drug pursued for treatment of neuropathic pain may show the way to healing multiple sclerosis lesions, according to early phase results.
A single injection of the agent ATL313 halted progression of paralysis in a rat model of MS for more than 80 days and "dramatically enhanced survival," researchers reported at the annual meeting of the Society for Neuroscience.
MS is typically accompanied by refractory chronic pain from inflammation of glial cells, making the novel agent -- which spurs immune cells to release potent anti-inflammatory cytokines in the central nervous system -- attractive for that reason.
But the researchers were more excited to see an apparent effect on scarring of the myelin sheath around nerves in the central nervous system since although drugs have been able to slow or stop disease progression they haven't resulted in healing of these characteristic lesions.
Specialized MRI scans of the spine of rats treated with ATL313 that had preserved motor scores indicated only minimal abnormalities whereas rats with low motor scores showed well-defined lesions. Further analysis to determine whether this represents healing of lesions is ongoing, according to the researchers.
-- C.P.
Military Helmet No Help in Blasts
Computer simulations by researchers at the Massachusetts Institute of Technology indicate that the U.S. military's standard-issue helmet does little to protect soldiers against brain injuries from explosive shocks -- but addition of a face shield could help, they said.
Shock-induced brain trauma is the most common serious injury to soldiers in Iraq and Afghanistan. According to the simulations, the helmet delays transmission of shock waves to the skull but doesn't attenuate them enough to make a difference. Moreover, it offers no protection at all when explosions occur in front of a soldier's face.
However, the MIT simulations, reported in Proceedings of the National Academy of Sciences, indicated that an integrated face shield could lower intracranial stresses from frontal shocks.
-- J.G.
New Target for Triple-Negative Breast Cancer
A potential new therapeutic target has emerged from laboratory studies of triple-negative breast cancer cell lines. A compound that inhibits two forms of the ADAM (a disintegrin and metalloprotease) enzyme reduced the growth of triple-negative cells by as much as 91%.
The compound also inhibited the cells' ability to migrate, Patricia McGowan, PhD, of University College Dublin in Ireland, reported at the recent Symposium on Molecular Targets and Cancer Therapeutics in Berlin.
In other experiments, McGowan and her colleagues examined the effects of treating triple-negative breast cancer cells with an inhibitor of ADAM and gefitinib (Iressa), which inhibits epidermal growth factor receptor (EGFR). The rationale for combining the two targeted agents came from recognition that ADAMs are involved in activation of EGFR binding proteins.
Simultaneous administration of the two compounds did not increase cell inhibition beyond what was observed with the ADAM inhibitor alone. However, adding gefitinib 72 hours after the ADAM inhibitor resulted in greater activity compared with simultaneous administration, although the difference did not reach statistical significance.
McGowan said she and her colleagues plan to expand their evaluation of ADAM inhibitors to other cancers that express one or more members of the EGFR family, including HER2, HER3, and HER4. Examples of such cancers include lung, colorectal, head and neck, and pancreatic cancers.
-- C.B.
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Sunday, November 28th 2010 at 4:37PM
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