Stem cells, typically from fertilized embryos, have been proposed as a method to treat many diseases but the ethics of using cells from embryos is a boiling pot of opinions and emotions. Stem cells have the potential to become any cell type which can replace damaged cells but stem cell sources are very limited. Even if embryonic stem cells could be used therapeutically, transplanting cells that are ‘non-self’ into a patient they will require dangerous immunosuppressant’s which have damaging side effects.
So what if we could get stem cells from other sources? What if we could get cells from the patients to remove the risk of rejection? Sounds good, let see how scientists are getting on.
Until recently it was thought that once a cell fate has been decided, it was stuck like that .In 2012 John B. Gurdon and Shinya Yamanaka received a joint Nobel Prize for their work in reverting a differentiated adult cell into a pluripotent cell, a type of stem cell that can differentiate into any cell type.
The aim of this type of research is to take cells from a patient induce a stem-like or pluripotent state and then treat them with biological compounds that will reprogram them into a different cell type. These induced Pluripotent Stem Cells, or iPSC’s are being researched such that they can be used therapeutically in many conditions such as Parkinson’s and retinal disease.
A recent study published in Cell Reports by Emborg’s group looked into removing skin cells also known as fibroblasts from Rhesus monkey models of Parkinson’s, culturing them with transcription factors to a pluripotent state and then using factors to turn them into brain cells.
Transcription factors are small proteins that bind DNA to either activate or repress a gene; by changing the levels of certain genes the cells type can be altered. Yamanaka’s ‘cocktail’ of transcription factors (oct4, sox2, klf4, and myc) is well established for reverting cells from differentiated adult cells to iPSC’s. Emborg uses these transcription factors to turn patient-specific skin cells into pluripotent stem cells and then use a specific culture medium (the liquid cells are grown in with certain special molecules and growth factors) biasing them to become neural cells.
Once these cells had grown for two weeks they were tested to show they were now neural cells. During growth they had turned into three cell types, the most important being dopamine producing neurones, the loss of which is the main cause of Parkinson’s. Once transplanted back into the Parkinson monkey model it was shown that the graft integrated well with no rejection issues. However there was no symptomatic improvement of the subjects. This could be due to the small graft size or inefficiencies in the protocol which could be solved with some tweaking.
As a proof of principle this paper works well as it shows that iPSC’s derived from a patient can be treated and implanted back as a different cell type but more work needs to be done. I think as we gain more knowledge about the brains physiology and about Parkinson’s disease, this type of therapy will be better suited to treat the disease.
If patient-specific therapy can be used to increase healthy cells that have been lost it can be used to treat not only Parkinson’s but also diabetes, sickle cell anaemia, motor neuron diseases among others. This treatment could, in our life time revolutionise medicine.
The Nobel Prize winning Yamanaka said: “My goal, all my life, is to bring this stem cell technology to the bedside, to patients, to clinic” something which is becoming more and more achievable.
Emborg, M. E., et al. (2013). “Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain.” Cell Rep 3(3): 646-650.
photo credit: <a href=”http://www.flickr.com/photos/mikeygottawa/374910126/”>Mikey G Ottawa</a> via <a href=”http://photopin.com”>photopin</a> <a href=”http://creativecommons.org/licenses/by-nc-nd/2.0/”>cc</a>
Emborg ME, Liu Y, Xi J, Zhang X, Yin Y, Lu J, Joers V, Swanson C, Holden JE, & Zhang SC (2013). Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain. Cell reports, 3 (3), 646-50 PMID: 23499447