Pluripotent stem cells have the ability to undergo self-renewal and to give rise to all cells of the tissues of the body. into specialized cell types dates back in 1961 when two scientists Drs. James A. Till a biophysicist and Ernest A. McCulloch a hematologist accidentally observed that this intravenous injection of bone marrow cells in previously irradiated mice led to the formation of colonies of proliferating cells in the spleen of those animals. The injected cells were blood-forming progenitor cells able to fully regenerate the blood cells and opening toward the clinical use of bone marrow transplantation for haematopoietic disorders . Isatoribine monohydrate Since then Isatoribine monohydrate the following works have reported the isolation identification and characterization of different types of stem cells. Today the field of stem cell research is usually in a rapid and dynamic growth representing one of the most exciting areas in life science. The importance of studying the biology of stem cells relies in their wide range of applications. In basic research stem cells symbolize a powerful system to study COL1A2 gene function and the physiological processes occurring during development. In biomedical research stem cells are used to study the pathogenesis of human genetic disease to identify new diagnostic and prognostic biomarkers and to test improved drugs. However what renders stem cell research extremely important is the vast potential of clinical applications of these cells. Their capacity to differentiate into specific cell types could be used in regenerative medicine to treat damaged or diseased tissues through cell-replacement therapies. Recently the US Food and Drug Administration (FDA) approved clinical trials using stem cells for the treatment of heart disease . Although some stem cell therapies are in clinical trials a lot more basic research is needed before therapies using differentiated stem cell-derivatives can be Isatoribine monohydrate applied in humans. Over the last years the major improvements and discoveries in stem cell research have been made in pluripotent stem cells (PSCs). The definition of pluripotent stem cell is based on two properties: self-renewal and potency. The self-renewal is the capacity of the stem cells to divide indefinitely generating unaltered cell daughters maintaining the same properties of the progenitor cell. In particular conditions or under specific signals a stem cell is able to exit from self-renewal and participate a program leading to differentiate into specialized cell types deriving from your three germ layers (ectoderm endoderm and mesoderm) . You will find two types of PSCs embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). ESCs are derived from the inner Isatoribine monohydrate cell mass (ICM) of preimplantation embryos [4 5 and can be indefinitely managed and expanded in the pluripotent statein vitroin vitrotechnology known as cell reprogramming [6 7 Similarly to ES iPS cells can be expanded indefinitely and they are capable to differentiate in all the derivatives of the three germ layers. The aim of this review is usually to provide a detailed overview of the recent discoveries in ESC and iPSC research. We will compare murine and human ESCs highlighting common and unique features of pluripotency. Particularly we will discuss the current notion of “ground state” of pluripotency for mESCs and whether such a na?ve state can exist for hESCs. Furthermore we will review the most recent advances in iPSCs and point out some key hurdles in cell reprogramming. Finally we will discuss the potential applications of pluripotent stem cells with a special emphasis on iPSCs as promising and exciting source to model human diseases and to develop cell-based therapies. 2 Embryonic Stem Cells 2.1 Mouse Embryonic Stem Cells: The “Ground State” of Pluripotency Murine ESCs (mESCs) were first isolated in 1981 from the ICM of mouse blastocyst the part that will give rise to the embryo. They can be maintained indefinitely in culture through self-renewing division and more importantly are pluripotent retaining the ability to differentiate into all somatic cell lineages . mESCs were originally established and maintained in presence of serum on mouse embryonic fibroblasts (MEFs) as feeder cells growing as round-shaped colonies of tightly packed cells suggesting close cell membrane contacts and inability to “walk” on the plate. Maintaining of the.