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Induced Pluripotent Stem Cells (iPS) - Blood Cells into Embryonic Pluripotent State
iPS or iPSC are derived from skin or blood cells that have been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes.

The discovery of embryonic stem cell (ESCs) from mouse as well as from human embryos has created more interest due to the pluripotency of the cells, that is their ability to produce any kind of cell in the body. They were engaged to transform the area of regenerative medicine in which unhealthy tissues or organs in an individual could be replaced by transplantation of cultured cells or an in-vitro produced tissue or organ. On the other hand its utilization has often been restricted by the fact that, if utilized for transplantation, the source of these cells (blastocyst from the donor) that is from a genetically dissimilar but of a similar species (allogenic), will be most probably recognised as non-self by the immune system of the recipient. Therefore utilizing the cells derived from embryonic stem cells for transplantation from an allogenic donor, may require a lifelong immunosupression and the problems associated with it. Further the reality that embryonic stem cells normally necessitate the utilization and destruction of blastocyst staged human embryos has important ethical issues.

The above hindrances have been resolved by an important breakthrough made by the team of Shinya Yamanaka in Japan. For about a period of ten years, Yamanaka worked on the likelihood of transforming somatic cells of adults into pluripotent stem cells. To carry out that task, he concentrated on a set of genes that were exclusively or greatly expressed in embryonic stem cells. The researchers in his group initially utilized retroviruses to over-express twenty four genes in fibroblasts of mouse and astonishingly after a few weeks afterwards they found that colonies greatly alike to usual mouse embryonic stem cells appeared in the cluster plates. In contrast to the initial fibroblast population, the resultant cells could be indefinitely maintained in culture and was able to function as embryonic stem cells. Furthermore they went still far to reveal that only a combination of four out of the twenty four genes, named oct 4, klf 4, sox 2 and cMyc (all of which code for the proteins that function as transcription factors to control the expression of diverse sets of genes) were adequate to induce nuclear reprogramming of somatic cells and to revert them to a primeval, pluripotent state. To differentiate these novel cells from their embryonic counterparts, they were mentioned as “induced pluripotent stem cells” or “iPS cells”. Later research showed that similar ideology could be applied to reprogram human somatic cells, a key move towards the long wanted utilization of pluripotent stem cells in the field of regenerative medicine.

Even though the initial investigations utilized the fibroblasts, scientists have revealed that various kinds of cells including cells from liver, stomach, pancreas, and also blood lymphocytes can be reprogrammed to become induced pluripotent stem cells. Further studies by the scientists have revealed that almost any kind of cell could be utilized as a potent target for reprogramming, excluding the thought that a rare progenitor or stem cell was the foundation for the production of an iPS cell. In an effort to recognize the biology of the reprogramming mechanisms, various researchers have tried to decode the function of each individual reprogramming factor. Even though yet not wholly understood, it revealed that cMyc gene has a distinct role from the other 3 genes, oct 4, klf 4, and sox 2. During the initial stages of nuclear reprogramming, cMyc is accountable for inducing the down regulation of genes usually expressed by differentiated somatic cells and at the same time initiating cellular metabolic changes. Oct 4, klf 4 and sox 2 seems to be significant in maintaining and establishing the stem cell gene expression program. About the dynamics of the reprogramming mechanisms, it is a comparatively slow process, utilizing a minimum of about eight to ten days of sustained expression of the reprogramming factors. In that period the endogeneous loci of genes that are significant in establishing a stem cell programme are remodelled to become actively expressed, whereas the expression of the reprogramming genes introduced through the viral vectors become silent. This feature might be principally essential for appropriated differentiation of the induced pluripotent stem cells.

It is well known that the enduring presence of the reprogramming factor transgenes (foreign genes) inside the genome of the established induced pluripotent stem cells, in which the reprogramming genes are not regulated by their usual or natural regulatory elements but by a viral or other regulatory elements, presents a strict complication for the use of this technology in the clinical field. But there is a huge potential for induced pluripotent stem cell research, where adult somatic cells such as skin, fibroblasts and peripheral blood cells can be collected effortlessly from any individual and can be utilized as the source for the production of personalised pluripotent stem cells. Subsequently, induced pluripotent stem cells can be engaged for the production of definite tissues or organs that can serve for the learning of any disease, monitor for novel therapeutic drugs or utilization in cell replacement therapy.

Exemplary illnesses that benefit from this technology includes, Amyotrophic lateral sclerosis (ALS), Inflammatory bowel disease (IBD), alpha -1 antitrypsin deficiency (AAT), Alzheimer’s Disease, Cystic fibrosis, Diabetes, Parkinson’s disease, cancer and so on. The practical revelation that induced pluripotent cells were in fact pluripotent was their capability to contribute to all kinds of tissues when injected in to immuno-compromised mice to form teratogens (tumors that include tissues from all 3 primary germ layers). Notably the mouse induced pluripotent cells were able to produce a whole mouse when injected into a mouse blastocyst. Pluripotent stem cells, similar to embryonic stem cells, have specific epigenetic prospect, which are significant for preservation of pluripotency. Production of induced pluripotent cells that are induced by Transcription factors requires total alteration of the epigenetic form of somatic cell into an embryonic stem cell like state. Therefore gathering evidence specifies that epigenetic processes not only play vital roles in the induced pluripotent cell production process, but also have an effect on the properties of reprogrammed induced pluripotent cells. Considering the functions of several epigenetic factors in induced pluripotent cell production also adds to our information of the reprogramming processes.

Induced pluripotent stem (iPS) cells have the prospective to alter drug discovery by supplying physiologically suitable cells for poisonous compound identification, target validation, compound screening, and tool discovery. The technique for producing induced pluripotent cells is marching speedily, as is the range of cell types that can be differentiated. Tissue-specific cells derived from induced pluripotent cells are presently being investigated by the pharmaceutical diligence for their use in recognition of cardiotoxic and hepatotoxic substances as therapeutically applicable systems for modelling cardiovascular, neurodegenerative and metabolic disorders, as well as for production of individual specific cell kinds.
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Induced Pluripotent Stem Cells (iPS) - Blood Cells into Embryonic Pluripotent State00