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The concept of Human Induced Pluripotent Stem Cells (HIPSC) is a new phenomenon, discovered through the work of Takahashi and Yamanaka in 2006. They showed that differentiated somatic cells, such as adult fibroblasts, can be induced to express pluripotency via the introduction of genes encoding the transcription factors Oct 3/4, Sox-2, c-Myc and KIf4 under cell culture. After nuclear programming, these somatic cells are now able to differentiate into all cell types. 36

The effect of HIPSC’s presents similarities to the results of NSC introduction into transgenic G93A-Mice. Has been reported that the systemic transplantation of IPSC’s into these mice extended their survival time by an average of 23 days compared to control. Furthermore, motor neuron loss was reduced significantly, these G93A mice displayed a 40% increase in the number of motor neurons present compared to control. Similarly, to mice treated with NSC, an increase in the secretion of the neurotrophin GDNF was also identified. 26

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These studies have demonstrated that induced pluripotent stem cells work very similar to neural stem cells and as such show potential for the use of regeneration of neural circuits and specific cells that extend survival in ALS patients. Induced pluripotent stem cells display distinct advantages over neural stem cell therapy, a significant advantage being, they overcome ethical concerns as IPSC’s are sourced from adult somatic cells. In turn, this will likely increase funding and support for scientists in their research for the treatment of degenerative disorders.  IPSC’s are also able to be sourced from the blood, providing greater availability and ease of access to scientists. Furthermore, as the cells are derived from the host, they overcome immune-rejection as the grafted cells are not recognised as foreign. IPSC’s also present advantages in drug development, their ability to differentiate into all cell types means they possible act as a source of testing, to assess drug toxicity. This reduces the cost of pre-clinical testing as well as the cost incurred using mouse models. By providing an assessment of their toxicity, they may be beneficial in providing information of the side effects drugs designed to treat ALS in the future.

Despite these advantages, IPSC’s also bring drawbacks. Firstly, to become pluripotent, these stem cells undergo nuclear programming through transcription factors such as c-Myc. C-Myc is an oncogene and its overexpression could potentially lead to the development of cancers through increased proliferation of cells. In addition, as viral vectors are often used for the delivery into the tissues, this brings risks as these viruses may integrate with the host’s own cells possibly leading to the formation of tumours. IPSC has been shown to have a very low efficiency rate, only a small percentage of somatic cells are programmed successfully into IPSC’s.

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