Help for Arteries in Renal Disease
Overcoming the endothelial dysfunction that contributes to high cardiovascular risk in chronic kidney disease might be as easy as an infusion, an animal study suggested.
In a rat model of chronic kidney disease, a systemic infusion of endothelial cells boosted nitric oxide levels after the cells homed in and took hold on vessel walls, Fadi Hage, MD, of the University of Alabama at Birmingham, and colleagues found.
The transfusion of cells from rat aortic endothelium led to better sensitivity and vasodilation in small vessels compared with sham-treated rats, the group reported at the American Society of Hypertension meeting in San Francisco.
"Transfusion of endothelial cells replenishes the damaged endothelium in nephrectomized rats and normalizes elevated systemic asymmetric dimethylarginine (ADMA) levels, releasing the inhibition of endothelial nitric oxide synthase, reversing chronic kidney disease-induced endothelial dysfunction," they explained.
-- Crystal Phend
A Good Reason Not to Tailgate
Give the driver in front of you some space -- breathing motor vehicle emissions may turn "good" HDL cholesterol into the "bad" LDL.
Mice exposed to two weeks of diesel emissions showed changes in HDL antioxidant and anti-inflammatory properties that correlated with damage in the blood and liver, according to Jesus Araujo, MD, from David Geffen School of Medicine at UCLA, and colleagues.
The damage was not reversed in the mice after a subsequent week of receiving filtered air, they wrote online in Arteriosclerosis, Thrombosis and Vascular Biology.
"This may be one of the mechanisms by which air pollution contributes to enhanced atherosclerosis," the researchers suggested.
-- Chris Kaiser
Choosing Stem Cells Holds Promise
Neural stem cells could play a therapeutic role in brain lesions, many researchers think, if only enough of them could take root in the damaged brain. Selecting the right cells in the first place could be the answer, according to Sushma Chaubey, PhD, of the Children's Hospital of Philadelphia, and John Wolfe, VMD, PhD, of the University of Pennsylvania.
The cells in question are those that carry a surface marker called CD15, which appears to play an important role in migration and in growth factor signaling, Chaubey and Wolfe reported in STEM CELLS Translational Medicine. Using fluorescence-activated cell sorting, the investigators were able to isolate a nearly pure population of CD15-positive. Those cells, in vitro, developed into all three major brain cell types -- neurons, astrocytes, and oligodendrocytes.
When they were injected into the brains of baby mice, their survival was significantly better than grafts that developed after injection of unenriched cells. The CD15-positive grafts showed all three cell types, but tended to produce more oligodendrocytes, which play a central role in protecting nerve cells. The increased survival of CD15-enriched cells "may be useful for therapeutic delivery in diseases with dispersed lesions," the researchers concluded.
-- Michael Smith
Possible New Attack on Progeria
Inhibiting an enzyme involved in the creation of the mutant protein responsible for the physical manifestations of Hutchinson-Gilford progeria syndrome might help improve the affected patients' condition, a mouse study suggested.
Progeria, which rapidly ages children and results in death at an average age of 13, is caused by the accumulation of progerin in cells throughout the body. Progerin is formed when a mutation causes the prelamin A protein to be farnesylated and methylated. An enzyme called isoprenylcysteine carboxyl methyltransferase (ICMT) is involved in the methylation.
Martin Bergö, PhD, of the University of Gothenburg in Sweden, and colleagues found that inhibiting ICMT in mice with a progeria-like disease increased the animals' body weight, improved grip strength, and prevented bone fractures and death. And, in cultured cells from children with progeria, reducing ICMT activity increased cell growth.
"Thus, targeting ICMT might be useful for treating prelamin A–associated progeroid disorders," the authors wrote in their paper in Science Express.
-- Todd Neale
Human Thymus Stem Cells Function in Mouse Model
Researchers have successfully used stem cells to replicate thymic epithelial cells that produce functional T cells, they reported in Cell Stem Cell.
"Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting," wrote Mark Anderson, MD, PhD, and Matthis Hebrok, PhD, both of the University of California San Francisco, and colleagues.
The researchers differentiated human pluripotent stem cells into thymic epithelial progenitors through regulation of multiple signalling pathways. The cells then matured into thymic epithelial cells that "produce T cells capable of in vitro proliferation as well as in vivo immune responses."
The authors cautioned in a statement that the process was successful in only 15% of mice.
If the procedure can be perfected, they noted, the stem cell-based thymic cells may have broad applications in immune-compromised patients and those receiving stem cell-based grafts.
-- Cole Petrochko
Outwitting a Deadly Brain Cancer
Combining radiation with the administration of an experimental ATM kinase inhibitor led to significant increases in survival in a mouse model of glioblastoma multiforme, a highly lethal form of brain tumor.
Targeting ATM kinase effectively turns off the tumor cells' ability to self-repair after being damaged by therapeutic radiation, according to Kristoffer Valerie, PhD, of Virginia Commonwealth University, who led the study. The treatment also limits cell proliferation and invasion, which are highly active processes in glioblastoma multiforme, and patients typically die within a year.
In a series of experiments, the researchers administered radiation, the ATM kinase inhibitor, or both to a group of mice with the tumors. Those that received the combination survived for more than 100 days compared with 35 days among those given a single treatment. And in a subgroup of mice whose tumors carried the p53 mutation, which is found in one-third of human glioblastoma, the animals survived for more than 200 days, and appeared to be "cured," the researchers reported in Clinical Cancer Research.
-- Nancy Walsh