Induced Pluripotent Stem (iPS) Cells


General description


Induced pluripotent stem (iPS) cells are cells obtained by reprogramming an ordinary somatic cell, such as skin derived fibroblasts, so that it regresses to a pluripotent state. Pluripotent stem cells have the ability for self-renewal and also the potential to differentiate into cells of all three germ layers (mesoderm, endoderm, ectoderm), being able to give rise to any somatic or germline cell type.

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iPS Cells Differentiation Potential


An extremely important advantage in comparison to embryonic stem cells (ESCs) is that it overcomes the ethical controversy related to this type of research. It also surmounts another major obstacle associated with ESCs, the immune rejection related to non-autologous stem cell transplantation.


History and Applications


iPS cells were first generated in August 2006, by inducing both mouse embryonic and adult fibroblasts via transduction of four transcription factors -- Oct4, Sox2, c-Myc and Klf4 -- using a viral vector (Takahashi and Yamanaka, 2006). Despite being capable of differentiating into cell types of the three germ layers, they lacked the ability to develop into germline precursor cells. Only in 2007, both germline transmission capability in mouse iPS cells and generation of iPS cells from human somatic cells was achieved. More recently in 2009, for the first time, cellular reprogramming was achieved without the potentially unsafe use of genetic material (Zhou et al., 2009), using recombinant cell-penetrating proteins which were able to induce mouse embryonic fibroblasts into a pluripotent state.

Pluripotent stem cells obtained by genetic and phenotypic reprogramming of human cells have a wide range of possible applications, being the most important ones autologous cell transplants and in vitro research of human diseases.

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iPS Cells Applications and Usage Lifecycle


Examples of more specific potential applications and benefits are:

  • Development of disease models;
  • Drug discovery and testing;
  • Conducting toxicity studies;
  • Autologous cell therapy for the regenerative treatment of a several diseases, e.g. Diabetes, Alzheimer's and Parkinson's disease, ALS, cancer, spinal cord injury, hematopoietic and immune disorders, neurological diseases, etc;
  • Tissue engineering and study of the underlying mechanisms of tissue development;
  • Cell lineage analysis.

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Treatment of mice with sickle cell anemia using iPS cells



Induction Factors


A number of studies have focused on the optimum number of transcription factors to be used for induction, trying to increase efficiency or determine the minimal set required. The genes usually used for pluripotency induction are the following:

  • Oct3/4
  • Sox2
  • Klf4
  • c-Myc
  • Nanog
  • Lin28


Patents


The Kyoto University in Japan was granted the first patent for iPS cells, covering only Japan, in September 2008 (patent 2008-131577), having filed its initial claim in December 2006. It also applied for an international patent (PCT/JP2006/324881) in December 2006. However, in January 2010, the Intellectual Property Office in the United Kingdom issued a Notification of Grant to iPierian, a California based company, for a UK patent (patent GB2450603), being this the first human iPS cells related patent to be granted outside of Japan.

To complicate matters, in March 2010 StemCells, Inc., another California company, acquired a new stem cell patent, this time for rats, in the United Kingdom (patent GB2451523). This in conjunction with the over 100 patents applications related to this type of technology presages a worlwide intellectual property battle.



References


  • Takahashi, K., Yamanaka, S., "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors", Cell, Vol 126, Issue 4, pp. 663-676, 25 August 2006
  • Zhou, H., et al., "Generation of Induced Pluripotent Stem Cells Using Recombinant Proteins", Cell Stem Cell, 23 April 2009
  • David Cyranoski, “Japan fast-tracks stem-cell patent “, Nature, 455, 269, published online 17 September 2008
  • Sabin Russell , “Britain grants patent for iPS cells”, Nature, published online 28 January 2010
  • “StemCells Scores New Stem Cell Patent (STEM)”, BioHealth Investor, published online 17 March 2010

By: Tiago Sanches, 43779

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