Transform Adult Cells into Embryonic State: Induced pluripotent stem cells

Induced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a “forced” expression of specific genes.

Induced Pluripotent Stem Cells are similar to natural pluripotent stem cells, such as embryonic stem (ES) cells, in many respects, such as the expression of certain stem cell genes and proteins, chromatin methylation patterns, doubling time, embryoid body formation, teratoma formation, viable chimera formation, and potency and differentiability, but the full extent of their relation to natural pluripotent stem cells is still being assessed.

iPSCs were first produced in 2006 from mouse cells and in 2007 from human cells. This has been cited as an important advance in stem cell research, as it may allow researchers to obtain pluripotent stem cells, which are important in research and potentially have therapeutic uses, without the controversial use of embryos. They also avoid the issue of graft-versus-host disease and immune rejection unlike embryonic stem cells because they are derived entirely from the patient.

The race to turn ordinary skin cells into embryonic stem cells – which can be used to make any tissue in the body – has ended in a dead heat, with two groups of scientists simultaneously announcing they have achieved the feat.

The breakthrough marks the beginning of a new era for stem cell biology and may spell the end for cloning as a way to produce stem cells.

Using the new technique, scientists were able to “rewind” adult skin cells back to their embryonic state. The process paves the way for the creation of stocks of stem cells that can be turned into any of the 200 or so types of tissue in the body.

The cells will first be used to study disease, by turning them into nerves, muscles and other tissues that carry the genetic defects associated with conditions such as Alzheimer’s and muscular dystrophy. Ultimately, embryonic stem cells may allow doctors to grow replacement organs and tissues that are genetically matched to patients.

Previously, scientists believed the only way to convert adult cells into embryonic stem cells was to clone them, a procedure that is extremely inefficient and involves the creation of an embryo that is destroyed when the cells are removed. The technique has attracted vehement criticism from pro-life groups, which oppose the use of embryos in research.

The new work may have its greatest impact in America where the Bush Administration has set stringent controls on stem cell research. Government-funded scientists are forbidden from working on stem cells created after August 2001, although privately funded researchers face no restrictions.

Modified viruses

In the latest research, the two teams used harmless, genetically modified viruses to smuggle a set of four genes into human skin cells. Once inside, the genes forced the cells to regress back to their embryonic state. Tests on the cells showed they were capable of forming any of the tissue types found in the body apart from egg and sperm cells.

Shinya Yamanaka, who led one of the teams at Kyoto University in Japan, first demonstrated the technique using mouse cells last year. Yesterday scientists were astounded at how quickly the work has been repeated in humans.

Dr Yamanaka reprogrammed skin cells from the face of a 36-year-old woman and other cells from the connective tissue of a 69-year-old man. For every 5,000 cells they treated, they created one batch of embryonic stem cells, according to the study published today in the journal Cell.

The second team, led by Jamie Thomson at the University of Wisconsin, converted immature skin cells taken from a human foetus and the foreskin of a newborn boy. Like Yamanaka, his team used four genes to reprogram the cells, but only two of the genes were the same as those used by the Japanese group. The American team’s work was published yesterday in the journal Science.

The new kind of stem cells are called “induced pluripotent cells”.

“The induced cells do all the things embryonic stem cells do,” said Prof Thomson, who was the first to extract embryonic stem cells from human embryos in 1998. “It’s going to completely change the field.”

Restored confidence

The studies are expected to restore confidence in the field of stem cell research, which slumped in 2005 after it emerged that a series of high-profile “breakthroughs” were nothing of the kind. The South Korean scientist Hwang Woo-Suk published two papers claiming to have created human embryonic stem cells from cloned embryos, and latterly to have made stem cells matched to individual patients.

Scientists still need to clear two major hurdles before the latest technique can be used to treat patients. First they need to find a different way to reprogram the cells: those made so far contain viral DNA that could easily cause mutations and possibly turn the cells cancerous. Once that hurdle has been overcome, scientists will need to perfect techniques for transforming stem cells into particular types of tissue.

Austin Smith, director of the Wellcome Trust Centre for Stem Cell Research in Cambridge, UK, described the latest research as a “major advance” and said it could make cloning experiments obsolete.

“The beauty of this is that it’s easier and almost anyone can do it. For the creation of stem cells, cloning is dead in the water,” he said.

“The only real hope for cloning was if for some reason human cells couldn’t be reprogrammed like this. But these groups have shown it works and it’s a process any cell molecular biologist can do. The main arguments for doing human cloning disappear because it’s technically incredibly demanding – only people with specialised expertise can do it, and there are huge issues about access to the material.”

source: guardian.co.uk

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