01 November 2009

Stem Cells: A Genetic Perspective

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The Plurigenes project, involving 7 European labs plus a start-up, impressed scientists around the world by showing that normal skin cells can be reprogrammed to an embryonic state in mice

Embryonic or neural stem cells are key tools for future studies on Parkinson’s disease or other degenerative diseases. So far, the only way to obtain embryonic stem cells implied the destruction of an embryo. Moreover, getting genetically matched cells to a those of a patient required cloning, which is ethically controversial. De-differentiating is of the issue here, if a completely novel approach is to be attempted.

The Plurigenes project, involving 7 European labs plus a start-up, already impressed scientists around the world by showing that normal skin cells can be reprogrammed to an embryonic state in mice.

Plurigenes researchers have been focusing on the central nervous system in order to discover how to control the de-differentiation of neural cells, with the purpose to generate pluripotent neural stem cells. These could, potentially, turn into any of the brain’s cells. The whole point of the project is, in order to take the first step towards regenerative medicine you need to learn how to control de-differentiation of adult tissue and understand the function of genes controlling pluripotency.

According to a further publication, researchers from the Plurigenes projects also identified a protein able to stop the growth of glioblastoma, which is a kind of brain tumour for which no cure is available yet. They suspect this kind of cancer is caused by cells with stem cell-like properties, which are able to reproduce and turn into all kinds of a tumour’s cells.

Plurigenes scientists concentrated on the study of BMPs, a protein controlling the differentiation of normal brain stem cells into a kind of brain cell called glial cell. By administering doses of BMP4 to mice affected by human glioblastoma, scientists noticed that these proteins effectively blocked the tumour’s growth and reduced mortality.

They also discovered that BMP4 does not kill stem cell-like tumour cells, but it forces them to differentiate into benign cells. This opens up a potential novel therapy for post-surgery glioblastoma patients.

Moreover, last autumn news came out that research conducted at the European Molecular Biology Laboratory (EMBL), one of Plurigenes’ partners, has helped scientists gain new insights into embryonic development. The project as a whole has used several animal models, and this time researchers, thanks to a newly developed microscope, were able to follow the first 24 hours in the life of a zebrafish from the single cell stage up to 20,000 cells.

Thanks to digital scanned laser light sheet fluorescence, they subsequently generated a three-dimensional digital representation of an almost transparent zebrafish embryo, which was defined as “the GoogleEarth of embryonic development”, allowing them to zoom in on every cellular and even subcellular detail of the first 24 hours of a fish. Their observations are unprecedented in as complex an organism as a vertebrate, and show that the fundamental movements of cells that later form the heart and other organs are different than previously assumed.

Zebrafish models are increasingly considered as very valuable in the study of embryonic development, toxicology and specific gene functions.

 

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