Every cell, off the peg

Insulin-making cells created by Dolly-cloning method

Cell replacement therapies could dramatically change treatments and even cure debilitating disease.
Stem cell medicine is coming of age but if we run with the Dolly method it will inevitably raise ethical concerns.

Source : Special report ‘Stem Cell Medicine’ of The Scientist May 2014


Every Cell, off the peg.

A revived cloning method has turned human adult cells into stem cells that can become anything you need, from neurons to cartilage.

The dream of generating a bank of stem cells to treat injury and illness is a step closer. Embryonic stem cells have been custom-made from adult cells without manipulating the cell셲 genes, a process that might trigger cancer.

Using a similar cloning technique to the one that created Dolly the sheep, two teams have independently shown that it is possible to turn an adult cell into an embryonic stem cell, which can then become any cell in the body.

One team used the technique, called somatic cell nuclear transfer (SCNT), to transform skin cells from a 35 and a 75-year-old man into stem cells. The other team went a step further, turning skin cells from a woman with diabetes into insulin-producing beta cells that could replace those destroyed by the disease. The approach has the potential to replace many other types of tissue including heart cells, neurons and cartilage. This could spur on treatments for Parkinson셲 disease, multiple sclerosis and liver disease, and repair damaged bones.

Cell replacement therapies could dramatically change treatments and even cure debilitating diseases and injuries. – Susan Solomon at the New York Stem Cell Foundation (NYSCF)

To achieve the feat, the teams one led by Young Gie Chung at the CHA University in Seoul, South Korea, and the other by Dieter Egli at the NYSCF first removed the nucleus of a donated human egg and replaced it with the nucleus from an adult skin cell. Caffeine was added to stop the cell dividing too quickly, buying time for the genes in the egg셲 new nucleus to revert to an embryonic state. Electrical pulses and chemicals fooled the cell into thinking it was fertilised, prompting it to divide and multiply.

The result was a bundle of 60 to 200 cells the first time an adult cell has been used to make a cloned human embryo. In the centre of the bundle were embryonic stem cells that can differentiate into any cell in the body, given the right environment.

In 2013, a similar procedure was used to convert cells from a fetus into embryonic stem cells. A fetus셲 cells are already essentially embryonic, so the latest work is a big step forward. Since the incidence of stem cell-treatable disease increases with age, researchers needed to figure out how to rewind adult cells, says Robert Lanza at Advanced Cell Technology in Worcester, Massachusetts, a co-author of the study led by the South Korean group (Cell Stem Cell, doi.org/sh2).

The approach offers an alternative to another method used to dial back the clock on adult cells. Induced pluripotent stem cells (iPS) are adult cells that have been coaxed into behaving like embryonic cells by adding four extra genes. There was a lot of excitement when iPS cells were first created in 2006, but since then serious problems have emerged, involving incomplete reprogramming of the cells and the worry that the extra genes might trigger cancer. They have overcome a lot of these problems, but SCNT might turn out to be the only way to fully reprogram cells.

To prove the potential of the technique, Egli셲 group took skin cells from a woman with type 1 diabetes and turned them into stem cells. These were then made into beta cells that could theoretically replace those lost to the disease (Nature, doi.org/sjn).

However, this personalised approach is unlikely to be the way forward. If the treatment was tailor-made for each patient, an embryo would have to be discarded every time. As well as the ethical objections this would raise, the procedure would be time-consuming, costly and would be limited by the small number of eggs donated. It is also unnecessary.

Stem cell bank

Donor cells are sometimes rejected because of our body셲 human leukocyte antigen (HLA)system. This produces proteins that are recognised by immune cells. If the proteins are not recognised, rejection occurs. Luckily, most people share one of a handful of HLA systems. That means you should only need to create stem cells specific to each HLA system, rather than each individual, says Lanza. Personalised stem cells would only be needed for people with uncommon HLA proteins.

Banks of stem cells could be created from just a handful of eggs. To make the process even more efficient, the embryonic stem cells could be transformed into the final product in advance, so heart cells or neurons, say, could be picked 쐎ff the shelf as needed.

Ian Wilmut of the University of Edinburgh, UK, who created Dolly the sheep, describes the work as very encouraging. He says that SCNT stem cells should now be compared with iPS cells to see which are the closest match to true embryonic stem cells created from fertilised embryos. By contrasting these two approaches, they will be able to optimise both procedures and produce the best possible cells for use in research and therapy.

This article tells high hopes for Dolly stem-cell technique.

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