ANTAGONIZING ATHEROSCLEROSIS

Antagonizing Atherosclerosis
France - Atherosclerosis or fatty plaque build up on the arterial wall is the source of most cardiovascular diseases. While B cells of the immune system were previously considered as elements of protection against the formation of these plaques, researchers from Inserm now refute this hypothesis. These findings were published online in the Journal of Experimental Medicine.

Atherosclerosis is an inflammatory disease of the arteries triggered by several factors, including increased cholesterol and characterized by an accumulation of lipids (fats) in the arterial wall in the form of plaques. The rupture of these plaques is responsible for the majority of cardiovascular diseases, like myocardial infarction or stroke. These diseases are the leading cause of death in industrialized countries. It is therefore essential to identify patients at risk and to understand the progression of the disease, to prevent and treat it.

The immune response (macrophages, B lymphocytes, T lymphocytes) which varies among
individuals plays an important role in the progression of these plaques and thus in the development of complications of cardiovascular disease. To date, the role assigned to all B cells seemed protective of atherosclerosis.

However, the work led by Ziad Mallat now clearly refute this hypothesis. The researcher showed in fact that using an antibody against B cells and causing the disappearance of 96% of
them provides significant protection against development of atherosclerosis. This antibody is
used very effectively in humans, in the treatment of certain inflammatory diseases. The protective effect is due to decreased production of an immune system hormone, interferon gamma which promotes atherosclerosis and increased interleukin-17 a protective hormone.

These findings have important clinical implications. They suggest that treatments directed against B cells currently administered to patients suffering from inflammatory diseases such as
lupus or rheumatoid arthritis, may reduce cardiovascular risk. Clinical trials have been undertaken in this direction by the team and aim to assess the extent of atherosclerosis before and after treatment.

Journal Reference:
Ait-Oufella, H., et al. B cell depletion reduces the development of atherosclerosis in mice. Journal of Experimental Medicine, 2010.
Link: http://jem.rupress.org/content/early/2010/06/30/jem.20100155

CREATION OF MICE FROM iPS CELLS

Live Mice Created from Adult Cells Reprogrammed

Mice were born and have even been able to procreate after being created from stem cells from reprogrammed adult cells, depending on the work of a Chinese team published in 2009.

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It is "the first definitive proof, to our knowledge, that the iPS cells are truly pluripotent, ie as versatile as embryonic stem cells, a characteristic" critical to therapeutic applications, "concluded by Qi Zhou (Chinese Academy of Sciences, Beijing) and his colleagues.

The ability of embryonic stem cells to differentiate to produce all types of human cells (blood, nerve, muscle ...) has made the challenge of medicine "regenerative" which would in future repair the heart or other organs, but their use raises ethical issues.

Thanks to the pioneering work in 2006 and 2007, Japanese researcher Shinya Yamanaka to program adult differentiated cells to become multi-purpose, cells induced pluripotent stem (iPS) are seen as an alternative to embryonic stem cells .

Since then, this technique was commonly used to reprogram the genomes of cells in a pluripotent state similar to embryonic cells, "recalls Qi Zhou in the study published online by the British scientific journal Nature.

To prove that the iPS cells are as versatile as embryonic stem cells, he showed that they could afford to produce live fertile mice.

Team Fani Qi Zeng and Zhou (Shanghai Jiao Tong University) has created 37 lines of iPS cells, three of which led to the birth of 27 mice, including the first-born named Tiny.

MAN-MADE: Tiny, live mice from iPS cells

One of them, a brown male adult was able to impregnate a female white coat and lead to second-generation mice in good health, according to researchers.

To produce viable mice, the researchers used as a cradle of biological cells called blastocysts with four sets of chromosomes (instead of two normal, one from the father and the other from the mother).

In this cradle (suitable for creating the placenta), they then injected iPS cells that have sent their own genetic heritage to all daughter cells forming the embryo. This proves, according to researchers, the iPS cells are pluripotent as embryonic stem cells.

Even if the cloning was not the objective of the experiment, it nevertheless leads to create animals with the same genetic program that the reprogrammed adult cells. The use of four sets of chromosomes (not both) to avoid mixing the DNA of the blastocyst, doomed to disappear, with iPS cells.

This technique avoids complex to create chimeras, animals whose cells all have the same genetic heritage. Small second-generation mice have uniformly brown coat, a sign that their parents are not chimeras, researchers stress.

At a press conference, they were encouraged to pursue "all forms of stem cell research, but are not limited to iPS cells."