About Stem Cells and the Holy Grail

A recent news article in Nature caught me into deep thoughts. The article reviewed some of the main developments in the field of induced Pluripotent Stem (iPS) cells. The formula seems simple: I have my “whatever” cell, and by introduction of a cocktail of genes, eventually I will find out that three or four genes are able to reprogramming the cell.

However, it seems that not every tale about iPS cells is so simple. Several issues are of the concern of scientists and medical doctors. For example, the efficiency of the production of the iPS cells, and the purity. Also, whether this cells will induce the formation of teratomas or tumours. I strongly recommend the News Article by Monya Baker in Nature [1] to read about the subject.

I share some of the enthusiasm about iPS cells. Working with primary cultures of stem cells is hard, slow and sometimes disappointing. For example, working with bone marrow derived stem cells is a slow process; from obtaining the sample until reaching a fourth passage, can take even four months, when cells are isolated from older donors (I worked with this model four years; I know what I’m talking about). If we can use these cells for the treatment of a disease, months can be lethal for the patient. Even so, cells are progressively loosing their “stemness”. iPS cells seems to circumvent some issues regarding efficiency. However, the artificial induction of a stemness state is a subject of relatively little study; by now, the focus of the scientists has been the improving of the methods for the development of the iPS cells, without worry about the mechanisms [1]. Then, the next step should be the further knowledge of mechanisms. In this scenario, Systems Biology should take an important place. We need to gain insight about what genes, what metabolic pathways, what proteins, what non-coding RNAs, what micro-RNAs, are being induced, are working, are being repressed.

From Bruneau Lab

From Bruneau Lab

Maybe a fresh approach is provided by the work by Takeuchi and Bruneau published online in Nature [2]. The authors showed that mouse mesoderm cells can be transdifferentiated into cardiac myocytes by the introduction of three genes: Gata4, Tbx5 (two cardiac transcription factors) and Baf60c (a cardiac-specific subunit of the BAF chromatin-remodelling complex). The novelty resides in that the authors further handle their work providing data about the mechanisms (something which is lacking in several other works): they show that Gata4 binds Tnnt2 and Nppa (cardiac genes) only in the presence of Baf60c, using chromatin immunoprecipitation. They even provide a model and a “minimal” regulatory gene network. This work can be considered a step forward in the way researchers are studying reprogramming. It is not a matter of just “we will insert these genes and quantify how fast the cells are induced to pluripotency”, but also the “how”. And it seems very reasonable thinking about the possible effect of the genes being introduced.

References

[1] News Feature Article:

Fast and Furious. M. Baker. Nature, 2009, Vol 458, pp. 962-965

[2] Takeuchi, J.K. and Bruneau B.G.

Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors.

Nature, 2009, doi:10.1038/nature08039

[3] Bruneau’s Lab Page (including videos):

http://web.mac.com/bruneaulab/Bruneau_lab/Welcome.html

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11 Responses to “About Stem Cells and the Holy Grail”


  1. 1 rendev August 8, 2009 at 11:24 am

    Hi
    Induced pluripotent stem (iPS) cells is an alternative methods for studying diseases that are more robust and better simulate how the disease develops in humans. The concerns expressed regarding chimerism may be a bit strong. Technological improvements with traditional ES cell microinjections have resulted in embryos which are 100% derived from the donor, not receipient, cells. Thus the first mice born are true clones of the source ES cells.
    Thanks!

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