Pluripotent stem cells differentiation

Zhang J et al (2009) Functional cardiomyo-cytes derived from human induced pluripotent stem cells. Circ Res 104(4) e30-e41 Zwi L et al (2009) Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation 120(15) 1513-1523 Burridge PW et al (2012) Production of de novo cardiomyocytes human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 10(l) 16-28 Rattman SJ et al (2011) Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and... 

P. W. Burridge, G. Keller, J. D. Gold, J. C. Wu, Production of de novo cardiomyocytes human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 10, 16-28 (2012). 

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. 

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... 

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... 

The potential contribution of stem cells to medical treatment lies in then-capability to differentiate and grow into normal, healthy cells. Using pluripotent stem cells, scientists are devising means to culture them in the laboratories and coax them to grow into various specialized cells. Rather than gene therapy, with stem cells we have the potential of cell therapy to repair our diseased tissues and organs. This will circumvent the lack of donor organs. Stem cells also provide the possibility for healthy cells to cure disabilities such as strokes, Parkinson s disease, and diabetes. 

Despite enormous progress, even today the hematopoietic system is not completely understood. However, it is agreed that all hematopoietic cells originate from a small population of pluripotent stem cells that proliferate and differentiate into the whole spectrum of mature blood cells (see Fig. 2) [1]. The pluri-... 

Both the B cells and T cells arise in the fetal liver or bone marrow (Fig. 31-1) from pluripotent stem cells. In birds the B cells develop in a special organ, the bursa of Fabricius. Mammalian B cells complete their differentiation into mature lymphocytes within the bone marrow. However, the T cells must travel to the thymus, where they complete their maturation. The T lymphocytes include the previously mentioned NK cells as well as the somewhat similar cytolytic T cells and immunoregulatory T cells. The latter are further characterized as helper T cells41 or suppressor T cells. The adaptive response requires cooperation of helper T cells in many instances. Tire mature B and T cells leave the bone marrow and thymus, which are known as the primary lymphoid tissues, and enter the blood circulation. Following "homing" signals42 they take up residence in a variety of locations... 

Pluripotent stem cells in the marrow give rise to more stem cells and to various progenitors. The lymphocyte progenitors give rise to B-cell and T-cell lineages. The final differentiation step in both B-cell and T-cell development requires antigenic stimulation. 

The cells of the immune system are formed from pluripotent stem cells produced in the bone marrow. These stem cells undergo a sequence of cellular differentiations to form B lymphocytes, T lymphocytes, erythrocytes, polymorphonuclear leukocytes, monocytes, macrophages, and mast cells. 

Fig. 6.11 The way is shown from a pluripotent stem cell to a multipotent, uncommitted colony-forming cell, to a committed colony-forming cell (CFO with an already restricted repertoire, and finally to a terminally differentiated blood cell. (For more information, see also ref. 30.)...

Cytokines have a central role in the differentiation of haematopoietic cell lines (the role of interleukins in the differentiation of lymphocytes will be discussed in more detail in Chapter 14). Haematopoiesis is the process by which terminally differentiated cells—red, white, and lymphoid blood cells—are continually formed from undifferentiated, pluripotent stem cells (Fig. 6.11). 

Stem cells. Embryonic and adult stem cells are distinguished. Embryonic stem cells are taken from an early stage of the embryo, such as from blastocytes. They are undifferentiated and totipotent. Their potential to differentiate and to form different cell lines is unlimited. Adult stemcells are taken from the blood forming bone marrow, from epithelial cells from the skin and other sources. They are pluripotent. Both, embryonic totipotent and adult pluripotent stem cells can replace functionally differentiated cells and tissues in the body. Stem cells can divide. After division, they may form again a stem cell or proceed to a final, fully differentiated state. 

MIC caused dose-dependent necrosis of brain cells and muscle cells (Anderson et al, 1988) of rats in culture these findings could explain neuromuscular complaints in Bhopal victims. Exposure of mice to 1-3 ppm MIC was found to inhibit erythroid precursors, pluripotent stem cells and granulocyte-macrophage progenitor recovery from this inhibitory effect was found within 3 weeks after 1 ppm but not after 3 ppm (Hong et al, 1987). At higher concentrations of 6-15 ppm, MIC inhibited cell cycling in bone marrow, alveolar cells, and T lymphocytes (Conner et al., 1987 Shelby et al, 1987) similar data were reported by others (Tice et al, 1987 Mason et al, 1987). MIC can inhibit bone marrow cell proliferation in mice (Meshram and Rao, 1988). MIC can cause necrosis in whole-brain cell cultures (Anderson et al, 1990) and inhibit differentiation in muscle cell cultures (Anderson et al, 1988). 

Differentiation is the developmental process by which early pluripotent cells acquire the features of late-stage, mature cells such as neurons, hepatocytes, or heart muscle cells. Currently, few examples of devised, highly selective, and efficient conditions for stem cell differentiation into specific homogeneous cell types have been reported because of a lack of understanding of stem cell signaling at the molecular level. Small-molecule phenotypic screens provide another means to generate desired cell types in a controlled manner. Several small molecules have been identified by this method that modulate specific differentiation pathways of embryonic or adult stem cells. 

Hematopoietic growth factors are glycoproteins produced by a number of peripheral and marrow cells. More than 200 billion blood cells are produced each day and the hematopoietic factors, along with other lymphopoietic factors such as- the. stem cell factor and the interleukins, are involved in the proliferation, differentiation, and maturation of various types of blood cells derived from the pluripotent stem cells. 

Differentiation Methods for Human Pluripotent Stem Cell-Derived Cardiomyocytes... 

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