The issue of stem cells is no doubt a hot topic, we hear about it in the news, in the papers and through medical based drama daily. From our beginnings as an embryo to the day we die our bodies contain active stem cells. These cells can be classed as either omnipotent or pluripotent. Embryonic stem cells as you may know are omnipotent; this provides the ability for any stem cell within the embryo to differentiate into any cell type, which in turn controls the development of every part of the body. If harnessed this potential could provide treatment for every known disease or serious injury, if you were in need transplant scientists could ‘grow’ one, if you have diabetes it could be treated signally instead of with daily blood checks and injections, in short such diseases and many more could be eradicated.

Similarly, pluripotent stem cells can be harvested from the cord blood at birth. Treatments have successfully been administered through this method however; there are significant limitations in that they are only applicable and successful if the stem cells are tissue typed to the person in need of treatment. This can be established in three limited ways: the storage of cord blood from birth (a process which is not accessible to everybody nor affordable); from a natural tissue match in the population or from a sibling (extremely unlikely). Through scientific intervention in reproduction and the use of Preimplantation Genetic Diagnosis along with HLA tissue typing, in order to select a match for implantation (saviour siblings).
A third group of stem cells can be derived from adult stem cells. To date there are a few adult stem cell treatments already in use such as bone marrow donation, however these do not contain pluripotency and must therefore be a specific match between donor and recipient and still presents the risk of rejection. The true potential of adult stem cells can only be developed through the inducement of pluripotency. Induced Pluripotent stem cells are essentially in their infancy with their discovery first being made in 2006 (Takahashi 2006) - ten years after the first embryonic stem cell line was developed. However, their potential to be developed as therapeutic treatments is immense.

Several research teams over the last three years have used genetic alteration to turn back the biological clock on adult somatic cells (cells which house our chromosomes) and create cells that are nearly identical to embryonic stem cells. The implications for disease treatment will be significant; generating a potentially limitless source of immune-compatible cells for tissue engineering and transplantation medicine.

The breakthrough came in October 2006, when a team led by Shinya Yamanaka, announced that they had reprogrammed mouse skin cells into cells that closely resembled embryonic stem cells, based on certain characteristic genes that were expressed. The reprogramming was achieved by introducing four genes essential for stem cell transcription. Oct 3/4, Sox2, c-Myc, and Klf4 were introduced into the skin cells with the help of a genetically engineered retrovirus. However, at this time Yamanaka was unable to verify that the cells were pluripotent.

In June 2007 Yamanaka's team, along with two others based in the US, reported that they had been able to provide the missing demonstration of pluripotency. The crucial step, of course, was being able to reprogram adult human cells in the same way, for all anyone knew this might be near impossible. However, later that year Yamanaka's team, together with another led by James Thomson (Junying Yu 2007), announced that this objective had been accomplished. Thompson’s team having the significant advantage of producing IPS cells with a new gene combination dispensing with c-Myc which is strongly linked with cancer (Takizawa 2007).

In 2008, this technology developed further with scientists creating mouse IPS cells to treat a mouse model of sickle cell anaemia and motor neurons from suffers of amyotrophic lateral sclerosis (ALS). These disease specific cells allow scientist a unique chance to study the development of a disease and test new treatments.

In 2009 several breakthroughs were announced. The first being more success in developing disease specific stem cells for research this time for spinal muscular atrophy (SMA). Scientists in Germany have been experimenting in finding one defining gene for inducing pluripotency and discover that Oct4 is the only gene required to develop neural IPS cells – work is still ongoing. Perhaps the most exciting is the development of a methodology which dispenses with the need for a viral vector when inducing cells. Dr Andras Nagy researchers in Toronto used a DNA transposon called a "piggyBac" to carry four genes that can transform mouse and human embryonic skin cells into iPS cells. After the conversion took place, the researchers removed the added DNA from the transformed cells using a specific enzyme. They are currently attempting this method with adult cells with the hope that it will have the same effect. If this is successful the elimination of the need for a viral vector will make IPS cells far safer and expand the research field by allowing many more labs to become involve whom have previously been restricted due to a lack of expertise necessary for working with viruses.

So How Will IPS cells Develop into a Cure?
Step 1:- Use somatic cells from patients with genetic diseases to create IPS cells

Step 2:- Observe and carry out research on these cells

Step 3:- Develop a treatment to ‘fix’ the broken gene causing the disease

Step 4:- Treat the patient with the ‘fixed’ stem cell to cure their disease

However, we are far from reaching this stage as science stands at the moment. Perhaps this is a good thing considering the lack of regulatory preparation apparent in many countries.

References

Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126:663–676

Junying Yu, A. Thompson. Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells. www.sciencexpress.org, 20 November 2007

Takizawa N, Yamanaka S, Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 30 November 2007

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