The supply of transfusable red blood cells (RBCs) is not sufficient in many countries. cell lines) able to produce transfusable RBCs were established they would be valuable resources. Our group developed a robust method to obtain immortalized erythroid cell lines able to produce mature RBCs. To the best of our knowledge this was the first paper to show the feasibility of establishing immortalized erythroid progenitor cell lines able to produce enucleated RBCs can also be established. 1 Introduction Transfusion therapies including RBCs platelets and neutrophils depend around the donation of these cells from healthy volunteers. However unpredictable adverse results can ensue from transfusion therapies because of the donation of cells from a very large number of anonymous volunteers. For example transfusion of blood products that include hazardous viruses or prions is usually difficult to prevent completely because occasionally assessments to detect them yield pseudo-negative results. There is little doubt that RBCs platelets and neutrophils produced would be candidate materials to replace cells donated from such a large group of anonymous individuals. The development of technologies such as PCR and gene knockout that enable the manipulation of an PF-4989216 organism’s genetic material contributed tremendously to progress in the life sciences in the final decades of the last century. This century looks to continue this progress through the development of further new technologies relating to cell manipulation. 2 Discovery of Plasticity in Terminally Differentiated Cells It was believed for a long time that epigenetic modifications in differentiated somatic cells were irreversible. This designed that terminally differentiated cells could by no means return to being immature cells. However in 1962 it was reported that this nuclei of somatic cells of an amphibian (frog) were reprogrammed following transfer into enucleated unfertilized eggs . Following transfer of a somatic cell nucleus the egg could undergo PF-4989216 cell division and differentiate to produce an adult frog. This result clearly indicated that epigenetic modifications in terminally differentiated somatic cells were reversible. Dr. John Gurdon who performed this groundbreaking study received the Albert Lasker Basic Medical Research Award in 2009 2009. In the beginning many biologists believed that this reversibility of epigenetic modifications in terminally differentiated cells was restricted to amphibian somatic cells and did not occur in mammalian somatic cells. However in 1997 a nuclear transfer experiment in sheep in which somatic PF-4989216 nuclei were transferred into unfertilized eggs showed that epigenetic modifications in terminally differentiated mammalian somatic cells were also reversible . This experiment famously resulted in the birth of PF-4989216 the first live cloned sheep named “Dolly”. 3 Immortalization of ES Cells The methodology for isolating and culturing mouse ES cells was first developed in 1981  and has aided research in a wide range of biological studies. Dr. Martin Evans who developed the technology for establishing mouse ES cell lines was awarded a Nobel Prize in 2007 together with Dr. Mario Capecchi and Dr. Oliver Smithies who developed homologous recombination technology in mouse ES cells. As a result of these technical improvements functional analysis of genes has progressed considerably using mice with gene knockouts or other genetic modifications. It is well known that mouse cells can be immortalized simply by continuous culture for example using the so-called “3T3 protocol”. One widely exploited example of an immortalized cell collection is usually NIH3T3 which continues to be used in a wide range of experiments. In contrast it is not possible to immortalize human somatic cells in KLRB1 a similar manner and this difficulty gave rise to the common assumption that it PF-4989216 would not be possible to establish human ES cell lines. However in 1998 17 years after the first establishment of mouse ES cell lines it was reported that human ES cell lines could also be produced by continuous culture . 4 Therapeutic Cloning The ability to.