An 'Inexhaustible Supply' of Adult Primary Cells?

Researchers from Georgetown University described a method for culturing adult primary cells that allowed them to keep dividing rapidly without dying or selecting for rare cells with stem cell properties. To keep most adult cells going in cell culture requires changing their gene expression. That means research on cultured cells is necessarily somewhat artificial, because cells need to have unusual characteristics to keep growing under current culture conditions. In their work, the authors used a combination of a Rho kinase inhibitor and feeder cells to keep several primary cell types growing in culture. The authors said, 'The efficiency and robust nature of establishing [conditionally reprogrammed cells] should greatly expand the value of biobanking and provide an inexhaustible supply of patient-specific cells for comparative genetic and molecular analysis.' The work was published in the Dec. 19, 2011, online issue of the American Journal of Pathology.

Anti-Aging Protein Protects from Huntington's

Two separate teams led by scientists from Harvard/MIT and Johns Hopkins University, respectively, have shown that longevity protein sirtuin1, or Sirt1, can protect neurons from the effects of mutant huntingtin. Previous work had shown that caloric restriction, which activates Sirt1 and increases life span, also protects against the effects of mutant huntingtin. In their new work, the authors showed that mice expressing mutant huntingtin were protected, to some extent, against developing Huntington's disease if they also were overexpressing Sirt1. Sirt1 knockouts developed worse symptoms. Sirt1 worked by preventing the decline in brain-derived neurotrophic factor. The work suggested manipulating Sirt1 levels could be a therapeutic strategy in Huntington's. Both papers were published in the Dec. 18, 2011, online edition of Nature Medicine.

Cytomegalovirus + Rabies = No Parkinson's

Researchers from the British University of Cambridge described a noncoding viral RNA that can protect dopamine neurons from the toxic effects of Parkinson's. Why such neurons die during Parkinson's disease is still not known, but dysfunctional mitochondria are clearly a harbinger of neuronal death. The authors showed that a noncoding RNA from cytomegalovirus protected mitochondria from Parkinson's damage. They were able to deliver the RNA to the brain via an I.V., by fusing it to a rabies virus glycoprotein peptide that enabled it to cross the blood-brain barrier. The authors said they believe their findings have major implications for Parkinson's treatment, 'especially given that this novel agent could have the same protective effect on all diseased neurons affected as part of this disease process.' The findings appeared in the Dec. 19, 2011, online edition of the Journal of Experimental Medicine.

Brain Cell Dysfunction Causes Heart Problems

Scientists from Baylor College of Medicine reported Rett syndrome patients may be prone to developing heart problems due to the lack of the protein MeCP2 in their neurons. Rett syndrome is a neurodevelopmental disorder characterized by autism-like symptoms and a shortened life span. About a quarter of deaths in those with Rett are sudden and of unknown causes. The authors showed that Rett syndrome mice have changes in their heartbeats that predispose them to develop unstable fatal heart rhythms, and that deleting MeCP2 specifically in their brains was enough to cause those changes. They said, 'Cardiac abnormalities in Rett syndrome are secondary to abnormal nervous system control.' The findings appeared in the Dec. 15, 2011, issue of Science Translational Medicine.

EETs Stimulate Cancer Metastases

Epoxyeicosatrienoic acids, or EETs, are metabolites that regulate inflammation and vascular tone, and drugs designed to raise EET levels are in clinical trials for hypertension, and other cardiovascular diseases. But scientists from Harvard University and the National Institute of Environmental Health Science discovered that any heart benefits of raising EETs may come at a high price. When they raised EET levels in mice with tumors, genetically or pharmacologically, the primary tumors grew faster and the animals tended to develop metastases in multiple organs. The increased metastases were not a direct result of the greater primary tumor growth but seemed to depend on the ability of EETs to influence endothelial cells in a way that made the metastasis sites more hospitable to rogue tumor cells. The authors said, 'Our data indicate a central role for EETs in tumorigenesis, offering a mechanistic link between lipid signaling and cancer and emphasizing the critical importance of considering possible effects of EET-modulating drugs on cancer.' The work appeared in the Dec. 19, 2011, online edition of the Journal of Clinical Investigation.

– Anette Breindl, Science Editor