Monthly Archive for April, 2011Page 2 of 2

Genetic abnormalities associated with the creation of stem cells

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Discovery sheds new light on the process of stem cell generation, and will help promote safer stem-cell based studies and future clinical trials.

Dr. Andras Nagy’s laboratory at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital and Dr. Timo Otonkoski’s laboratory at Biomedicum Stem Cell Center (University of Helsinki), as well as collaborators in Europe and Canada have identified genetic abnormalities associated with reprogramming adult cells to induced pluripotent stem (iPS) cells. The findings give researchers new insights into the reprogramming process, and will help make future applications of stem cell creation and subsequent use safer. The study was published online today in Nature.

The team showed that the reprogramming process for generating iPS cells (i.e., cells that can then be ‘coaxed’ to become a variety of cell types for use in regenerative medicine) is associated with inherent DNA damage. This damage is detected in the form of genetic rearrangements and ‘copy number variations,’ which are alterations of DNA in which a region of the genome is either deleted or amplified on certain chromosomes. The variability may either be inherited, or caused by de novo mutation.

“Our analysis shows that these genetic changes are a result of the reprogramming process itself, which raises the concern that the resultant cell lines are mutant or defective,” said Dr. Nagy, a Senior Investigator at the Lunenfeld. “These mutations could alter the properties of the stem cells, affecting their applications in studying degenerative conditions and screening for drugs to treat diseases. In the longer term, this discovery has important implications in the use of these cells for replacement therapies in regenerative medicine.”

“Our study also highlights the need for rigorous characterization of generated iPS lines, especially since several groups are currently trying to enhance reprogramming efficiency,” said Dr. Samer Hussein, a McEwen post-doctoral scientist who initiated these studies with Dr. Otonkoski, before completing them with Dr. Nagy. “For example, increasing the efficiency of reprogramming may actually reduce the quality of the cells in the long run, if genomic integrity is not accurately assessed.”

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Kidneys created from stem cell

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It raises hopes that kidney disease patients will one day be able to grow their own new organs with no risk of rejection.

Kidneys 5mm long – the size of those in foetuses – were made using a combination of cells from amniotic fluid, which surrounds babies in the womb, and animal foetal cells.

It is hoped the organs could be grown to maturity if implanted in a patient. In future, people’s amniotic fluid could be retained at birth, allowing it to be used later if they develop kidney disease.

‘The idea is to start with human stem cells and end up with a functioning organ,’ said physiologist professor Jamie Davies, whose University of Edinburgh team carried out the work.

‘We are working on how you turn cells floating about in liquid into something as precisely arranged as a kidney. We have made pretty good progress with that.

‘We can make something that has the complexity of a normal, foetal kidney but not an adult one yet.’

Stem cell technology could be ready for use on humans in about ten years, he said.

A US team has already shown a foetal kidney can be put into an adult animal and grown there. About 7,000 people are on the waiting list for kidney transplants but there is a serious shortage of the organs.

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