Monday, October 10, 2011

Creating stem cells can now be up to 100 times faster

By modifying an existing technique, scientists have found a way to increase the stem cell production in the lab by 100-fold. In addition, the created cells are of higher quality, compared to the old technique. By increasing quantity and quality, scientists gain more options to use stem cells in experimental treatments that focus on regeneration of tissues. Before, artifically creating cells with the capability to differentiate into many cellular lineages was a difficult and slow process with low yields. By updating the method to create stem cells, research in this field has just been made a whole lot easier, possibly speeding up development of novel stem cell treatments, for example to counter neurodegenerative diseases which we are currently unable to repair.
Currently, making stem cells from ordinary cells is based upon reprogramming them by incorporating four extra genes into their genome: Originally, Oct3/4, Sox2, Klf-4 and C-Myc, were used to create the first stem cells of this kind, so-called induced pluripotent stem cells (iPS). The technique, developed years ago, revolutionized stem cell research, as it was no longer necessary to use stem cells from embryos. Because C-Myc and Klf-4 can cause cancer, the cocktail of genes was later modified to just Oct4, Sox2 and a new player, called Nanog. While this did prevent development of cancer, this also decreased the production speed and yields.

Though all these names may not ring a bell to most, they are the cornerstones of artificially creating stem cells, without having to tap into controversial and sometimes prohibited sources, like embryo-derived stem cells. In most cases, scientists start of with a specific type of skin cell, called a fibroblast, which is to be reprogrammed into a stem cell by genetic modification. To get the genes into the DNA, viruses carrying the gene of interest are used. The picture below shows the whole process in a nutshell, with the addition of another technique: inserting the genome of adult cells into empty egg cells or very primitive embryonic cells, to create a clone with the same DNA of the organism that provided genome. The latter process is an alternative to creating primitive cells, but is rarely used anymore.
The scientists made the existing method more efficient by adding some extra factors to the mix. Next to using the four genes that form the 'golden standard' of creating iPS cells, the factors retinoic acid receptor gamma (RAR-γ) and liver receptor homolog (Lrh-1) were added to the mix. While the names suggest they have a function in the eye and the liver, it is not uncommon that proteins are named after the organ in which they were originally discovered, after which their full functionality is unraveled.

With six factors introduced into the genome, fibroblasts were reprogrammed into iPS cells a 100-fold more efficient than with the four original factors. With this, the researchers have tackled one of the biggest problems of iPS: making them in the lab takes long, and is a difficult process. In addition, the yields were usually very low. Next to cranking up the yield, the quality of the cells was also much higher: this is probably due to increased capability to guide the differentiation process of the stem cells into tissue of choice.

If the new technique can be generally applied, iPS cells have gained another advantage over other sources of stem cell research. However, embryonic stem cells have also recently benefited from a scientific breakthrough: it is now possible to create embryonic stem cells in the lab, without having to obtain them from an actual embryo, which is still controversial. To achieve this, the genetic material of a fibroblast was inserted into an unfertilized egg, similar to the SCNT technique shown in the picture above. The downside is that these cells contain too much genetic information: the full adult genome of the fibroblast, and the genetic material of the unfertilized egg. Therefore, this method is currently not suitable for clinical use.

By producing more and higher quality iPS cells, we could be able to develop tissues faster and more effectively, which reduces time needed to get regeneration treatments based on stem cells into the clinic. 

No comments:

Post a Comment