Cells for New life
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Types of Stem Cells

Induced Pluripotent Stem Cells

Induced pluripotent stem cells (iPSC)

Stem cells of this kind do not normally exist in nature. They were created artificially to study possibilities of growing in vitro tissues and organs immunologically and individually compatible with the patient's organism. The topic being difficult for understanding, one should first get aware of related technicalities.

During mammalian development, cells gradually lose potential and become progressively differentiated to fulfill the specialized functions of somatic tissues. For example, only zygotes and blastomeres of early morulas retain the ability to give rise to all embryonic and extra-embryonic tissues, and are therefore called “totipotent”, while cells of the inner cell mass of the blastocyst can give rise to all embryonic but not all extra-embryonic tissues, and are hence called “pluripotent”. Cells residing in adult tissues, such as adult stem cells, can only give rise to cell types within their lineage and are called either “multipotent” or “unipotent”, depending on the number of developmental options they have. Upon terminal differentiation, cells entirely lose their developmental potential.

In other words, the totipotent cell can support the development of an entire human organism, the pluripotent cell evolves into all cell types existing in human organism, the multipotent cell provides only several cell types within one type of tissue, and unipotent – only one type of special-purpose cells. The idea of induced pluripotent cells creation is about obtaining the line of pluripotent cells from a mature special-purpose cell or an adult stem cell. For example, if you take patient's skin fibroblasts (which are mature cells) and reprogram those in such way, that they would become pluripotent, to obtain any cell from them i.e. neurons, cardiac myocytes, hepatocytes etc.  And moreover, such neurons, cardiac myocytes, or hepatocytes would not be rejected by the patient's organism as they represent the exact genetic match to it. Such a process is called therapeutic cloning.

During the 1950s, Briggs and King established the technique of stem cell nuclear transferring, or “cloning” to probe the developmental potential of nuclei isolated from late-stage embryos and tadpoles by transplanting them into enucleated oocytes. This work showed that differentiated amphibian cells indeed retain the genetic information necessary to support the generation of cloned frogs. The major conclusion from these and subsequent findings was that development imposes reversible epigenetic rather than irreversible genetic changes on the genome during cellular differentiation. The cloning of Dolly, the sheep and other mammals from adult cells, including terminally differentiated cells, showed that the genome of even fully specialized cells remains genetically totipotent i.e. can support the development of an entire organism. Such a process is called reproductive cloning. However, most cloned animal’s exhibit subtle to severe phenotypic and gene expression abnormalities, suggesting that stem cell nuclear transferring results in faulty epigenetic reprogramming.

While stem cell nuclear transferring is a powerful tool to probe the developmental potential of a cell, it is technically challenging and not well suited for genetic and biochemical studies. Thus, another major advance toward isolating iPSCs was the establishment of immortal pluripotent cell lines from terato-carcinomas, tumors of germ cell origin. These cell lines were called embryonal carcinoma cells and could be clonally expanded in culture while retaining pluripotency. Importantly, when embryonal carcinoma cells were fused with somatic cells, such as thymocytes, the resulting hybrid cells acquired biochemical and developmental properties of embryonal carcinoma cells and extinguished features of the somatic fusion partner. The dominance of the pluripotent state over the somatic state in hybrids suggested that soluble trans-acting factors must exist in embryonal carcinoma cells that can confer a pluripotent state upon somatic cells, and that these factors should be identifiable.