Pluripotent stem cells

There are two general avenues for stem cell research pluripotent and multipotent stem cells. Pluripotent stem cells are obtained by two methods. One method is to harvest the clusters of cells from the blastocysts of human embryos. Another method is the isolation of pluripotent cells from fetuses in terminated pregnancies. Multipotent stem cells are derived from umbihcal cords or adult... 

Boheler KR (2009) Stem cell pluripotency a cellular trait that depends on transcription factors, chromatin state and a checkpoint deficient cell cycle. J Cell Physiol 221(1) 10-17... 

Stem cell. Pluripotent cells, representing 0.01% of bone marrow cells, having the capacity for self-renewal and committed to differentiate along particular lineages, e.g. erythroid, megakaryo-... 

Differentiated Cells Endothelial Progenitors Smooth Muscle Progenitors Mesenchymal Stem Cells Pluripotent Stem Cells... 

All mature blood cells arise from primitive hematopoietic cells in the bone marrow, the pluripotent stem cells. Approximately 0.1% of the nucleated cells of the bone marrow are pluripotent stem cells and approximately 5% of these cells may be actively cycling at any one time. The stem cell pool maintains itself through a process of asymmetrical cell division when a stem cell divides, one daughter cell remains a stem cell and the other becomes a committed colony-forming cell (CFC). The proliferation and differentiation of CFCs are controlled by hematopoietic growth factors. The hematopoietic growth factors stimulate cell division, differentiation and maturation, and convert the dividing cells into a population of terminally differentiated functional cells. 

Osteoclasts are multinucleated cells derived from pluripotent hematopoietic stem cells. Osteoclasts possess an apical membrane domain, exhibiting a ruffled border that plays a key role in bone resorption (Figure 48-12). A proton-translocating ATPase expels protons across the ruffled border into the resorption area, which is the microenvironment of low pH shown in the figure. This lowers the local pH to 4.0 or less, thus increasing the solubility of hydroxyapatite and allowing demineralization to occur. Lysosomal acid proteases are released that digest the now accessible matrix proteins. 

Erythropoiesis is a process that starts with a pluripotent stem cell in the bone marrow that eventually differentiates into an erythroid colony-forming unit (CFU-E)4 (Fig. 63-1). The development of these cells depends on stimulation from the appropriate growth factors, primarily erythropoietin. Other cytokines involved include granulocyte-monocyte colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3). Eventually, the CFU-Es differentiate into reticulocytes and cross from the bone marrow into the peripheral blood. Finally, these reticulocytes mature into erythrocytes after 1 to 2 days in the bloodstream. Throughout this process, the cells gradually accumulate more hemoglobin and lose their nuclei.4... 

Hematopoiesis is defined as the development and maturation of blood cells and their precursors. In utero, hematopoiesis may occur in the liver, spleen, and bone marrow. However, after birth, it occurs exclusively in the bone marrow. All blood cells are generated from a common hematopoietic precursor, or stem cell. These stem cells are self-renewing and pluripotent and thus are able to commit to any one of the different lines of maturation that give rise to platelet-producing megakaryocytes, lymphoid, erythroid, and myeloid cells. The myeloid cell line produces monocytes, basophils, neutrophils, and eosinophils, whereas the lymphoid stem cell differentiates to form circulating B and T lymphocytes. In contrast to the ordered development of normal cells, the development of leukemia seems to represent an arrest in differentiation at an early phase in the continuum of stem cell to mature cell.1... 

BIX01294, which inhibits G9a [29], is efficacious as a replacement for oct3/4, one of the four original genetic factors used for reprogramming of mammalian somatic cells into induced pluripotent stem cells [36]. 

Takahashi K, Tanabe K, Yamanaka S et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131 861-872... 

Knowledge gained from cell adhesion studies with SAMs has been used to develop culture substrates with the appropriate cell adhesion glycoproteins for different types of cells [7-10], Stem cells, capable of self-renewal and differentiation into multiple cell types, are found in embryonic and adult tissues. Pluripotent stem cells, like embryonic stem cells and induced pluripotent stem cells, have been developed in vitro. These cells are expected to provide cell sources for regenerative medicine. Various culture conditions have been developed to enable expansion of these cells without loss of their multi- and pluripotency and to induce differentiation into viable cells with specific functions. 

Cell transplantation has shown promise as a method for treating serious diseases. Various kinds of pluripotent stem cells have been developed or identified, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs). Moreover, the differentiation of stem cells to functional cells has been extensively studied. Previous studies have demonstrated that the transplantation of islet of Langerhans cells (islets) could successfully treat type 1 diabetes. Islets are insulin-secreting cells found in the pancreas. Over 200 patients... 

Ronaghi M, Erceg S, Moreno-Manzano V, Stojkovic M (2010) Challenges of stem cell therapy for spinal cord injury Human embryonic stem cells, endogenous neural stem cells, or induced pluripotent stem cells Stem Cells 28 93-99... 

Mylotarg (like most other drugs) does induce some side effects, the most significant of which is immunosuppression. This is induced because certain additional (non-cancerous) white blood cell precursors also display the CD33 antigen on their surface. The immunosuppressive effect is reversed upon termination of treatment, as pluripotent haematopoietic stem cells (Chapter 10) are unaffected by the product. 

The trial entailed retroviral-mediated ex vivo transduction of haematopoietic stem cells from 10 young SCID-X1 sufferers, with subsequent re-infusion of the treated cells. A marked and prolonged clinical response in which the condition was essentially reversed was observed in 9 out of the 10 patients. The prolonged response was likely due to the transduction of pluripotent progenitor cells with self-renewal capacity (Chapter 10). However, the two youngest patients (1 and 3 months old at the time of treatment) developed uncontrolled proliferation of mature T-lymphocytes 30 months and 34 months after gene therapy respectively. 

Cumano, A. and Godin, I. Pluripotent hematopoietic stem cell development during em-bryogenesis, Curr. Opin. Immunol., 13, 166, 2001. 

Figure 2.1. Development of blood cells. The development of blood cells occurs in the bone marrow. All cells arise from the differentiation of pluripotent or multipotent stem cells, which have the capacity for self-renewal, or else can divide into more mature cells types. The morphological features of the mature blood cell types is shown.

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