Stem cells cell fusion

McIntosh KR et al (2009) hnmunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model. Tissue Eng Part A 15(9) 2677-2686... 

Cell fusion may underlie some observations of grafted cells 514 COMMON STEM CELL THERAPY CHALLENGES 514 CONCLUSIONS 514... 

The functions of these fusion proteins and their precise roles in the induction of cancer are currently the subject of intense investigation (Collins et al., 2006 Huntly et al., 2004 Kindle et al., 2005). In general, it appears that since the proteins are fused in-frame, their catalytic domains continue to function, but these activities are mis-directed by the targeting domains of their fusion partners. The result is aberrant acetylation of chromatin and non-chromatin proteins, as well as sequestration of key nuclear regulators. These mechanisms are discussed in-depth in Chapter 8 of this book. Furthermore, two recent studies have demonstrated that wild-type MOZ is essential for development of hematopoietic stem cells (Katsumoto et al., 2006 Thomas et al., 2006). This suggests that AML may arise not only due to the aberrant activity of the fusion proteins, but also due to the loss of their original function. 

Skeletal myoblasts are adult, tissue-specific stem cells [73] located between the basal lamina and the sarcolemma on the periphery of the mature skeletal-muscle fiber [74]. Also known as muscle satellite cells, these small, mononuclear cells are activated by biochemical signals to divide and differentiate into fusion-competent cells after muscle injury. 

Imatinib (STI571) is an inhibitor of the tyrosine kinase domain of the Bcr-Abl oncoprotein and prevents the phosphorylation of the kinase substrate by ATP. It is indicated for the treatment of chronic myelogenous leukemia (CML), a pluripotent hematopoietic stem cell disorder characterized by the t(9 22) Philadelphia chromosomal translocation. This translocation results in the Bcr-Abl fusion protein, the causative agent in CML, and is present in up to 95% of patients with this disease. This agent inhibits other activated receptor tyrosine kinases for platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF), and c-kit. 

Chronic myelogenous leukemia (CML) arises from a chromosomally abnormal hematopoietic stem cell in which a balanced translocation between the long arms of chromosomes 9 and 22, t(9 22), is observed in 90-95% of cases. This translocation results in expression of the Bcr-Abl fusion oncoprotein with a molecular weight of 210 kDa, which is constitutively expressed. The clinical symptoms and course are related to the white blood cell count and its rate of increase. Most patients with white cell counts over 50,000/ L should be treated. The goals of treatment are to reduce the... 

Ren J, Ge L, Li Y, Bai J, Liu WC, Si XM. Detection of circulating CEA molecules in human sera and leukopheresis of peripheral blood stem cells with E. coli expressed bispecific CEAScFv-streptavidin fusion protein-based immuno-PCR technique. Ann NY Acad Sci 2001 945 116-118. 

The development of a stem cell into cells with specialized function is called the process of differentiation. This takes place most dramatically in the development of a fetus, from the single cell formed by the fusion of one spermatozoon and one ovum to a vast array of different tissues. 

Imatinib. Chronic myelogenous leukemia (CML) results from a genetic defect in the hematopoietic stem cells of the bone marrow. Nearly all CML patients possess the Philadelphia chromosome. It results from translocation between chromosomes 9 and 22 of the c-abl protooncogene, leading to the hybrid bcr-abl fusion gene on chromosome 22. The recombinant gene encodes a tyrosine kinase mutant with unregulated (constitutive), enhanced activity that promotes cell proliferation. Imatinib is a tyrosine kinase inhibitor that specifically affects this mutant but also interacts with some other kinases. It can be used orally in Philadelphia chromo-some-positive CML. 

A. and Chambers, L, The homeodomain protein Nanog and pluripotency in mouse embryonic stem cells, Biochem. Soc. Trans. 33, 1518-1521, 2005 Silva, J., Chambers, L, Pollard, S., and Smith, A., Nanog promotes transfer of pluripotency afer cell fusion. Nature 441, 997-1001, 2006. 

The molecular evidence for the descent of the eukaryotes (Hartman and Fedorov, 2002) is deeply controversial (see Section 8.01.6.3). Standard models (Woese, 1987) suggest an ancestral hne among the Archea, with massive transfers and symbioses from the bacteria. The standard model (e.g., see summaries in Pace (1997) Nisbet and Fowler, 1996a,b) is that early archaea and bacteria diverged from a hyperthermophile last common ancestor. Then, a sequence of symbiotic events took place between a stem-cell line, among the archaea, that developed partnerships with symbiotic purple and cyanobacteria, either in separate events, or in a single moment of fusion. This produced the eukaryote cell, with the mitochondria derived (Bui et al., 1996 from within the a-proteobacteria such... 

One approach to overcome the transplant rejection of human embryonic stem (ES) cells is to derive them by nuclear transfer of the patients own cells. In the absence of an efficient protocol for human somatic cell nuclear transfer (SCNT), several critical steps must be optimized, namely reprogramming time, activation method, and in vitro culture conditions. Reprogramming time was defined as the time between cell fusion and oocyte activation to permit proper embryonic development. A 2 h reprogramming time led to 25% of the recon-stracted embryos developing to blastocysts. In SCNT, in the absence of sperm-mediated activation, an artificial stimulus is needed to initiate embryo development. Addition of 10 pM ionophore for 5 min, and incubation with 2.0 mM 6-dimethyl aminopurine for 4 h, was the most efficient chemical activation protocol for human SCNT embryos. Encouragingly, inefficiencies in embryo culture have been overcome by supplementing... 

Germ-line cells and rapidly dividing somatic cells (e.g., stem cells) produce telomerase, but most human somatic cells lack telomerase. As a result, their telomeres shorten with each cell cycle. Complete loss of telomeres leads to end-to-end chromosome fusions and cell death. Extensive shortening of telomeres Is detected as a kind of DNA damage, with consequent stabilization and activation of p53 protein, leading to p53-trlggered apoptosis. 

This particular phenomenon may provide information as to how the liver provides niches for facultative stem cells or offers an opportunity for cell fusion [19]. 

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