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"You take the blue pill - the story ends, you wake up in your bed and believe whatever you want to believe. You take the red pill - you stay in Wonderland and I show you how deep the rabbit-hole goes." -Morpheus
Thus begins the journey of Neo in 1999 Hollywood blockbuster The Matrix. The hero prophesised to be 'the one' had to make a choice would change his future. As happened with Neo cells too make choices.
We have over 200 different types of cell in our bodies. All of these came from the embryonic stem cell. This one cell divides and with each generation the daughter cells become more specialised. It is obvious that each stem cell in the embryo cannot randomly differentiate into cell type otherwise there would be chaos! Thus each stem cell1 has a set of instructions or genes that tell that stem cell what type of cell to turn into. Scientists call these instruction genes 'master regulator' genes. One example such a gene is GATA1 that when switched on tells bone marrow stem cells to become red blood cells. There are also genetic instructions that tell the stem cell and its daughter cells when to stop dividing. When these instructions are not read properly by proteins in the nucleus healthy cells carry on dividing and become cancer cells.
Understanding how stem cells divide and the genes involved has lead to exciting medical breakthroughs. One of the most exciting areas of medical research at the moment is making 'new' embryonic stem cells rather than using discarded embryos from IVF clinics. These new cells are made by giving skin cells the genetic instructions to turn back into embryonic stem cells. This works because stem cells have special genes switched on that cause them to stay as stem cells when they divide. Scientists have found that putting these genes in skin cells causes them to become embryonic stem cells that have been called 'induced pluripotent stem cells' (iPSC). These developments are exciting for a number of reasons.
Firstly it may in the future allow doctors to make new organs for patients from embryonic stem cells that were skin cells. This would provide organs for the 7,800 patients in the UK waiting for an organ transplant2 (March 2011). Secondly many people find using discarded embryos for medical use to be ethically unacceptable. These iPSC cells would allow patients to accept embryonic stem cell treatments whilst having a clear conscience. Lastly this research has allowed many more scientists to carry out research on human stem cells. Rather than scientists having to use animals to study stem cells, they can now make human stem cells in the laboratory. Drug researchers will likely be able to make a human organ and use that organ model to test drug effectiveness and safety. This will help develop much more effective and safer drugs in the future and avoid tragedies such as that of the drug TGN1412. This drug was made by pharmaceutical company TeGenero and nearly killed 6 volunteer patients in a phase I clinical trial at Northwick Park hospital in 20063. TGN1412 targets immune cells and passed safety trials in monkeys. It failed because though monkeys are our closest evolutionary relatives, there are small differences between their immune systems and that of humans.
There remains a lot to be understood about stem cells. One of the main challenges facing researchers is that some stem cells do live for long outside the body, possibly because they require contact with the collagen scaffold that holds tissues and organs together. These challenges in unserstanding stem cells are also opportunities. Solving them will reshape the future of medicine. Stem cells may be the Neo that we have all been waiting for.
