Human somatic cell

Use of rodent or human somatic cell hybrids Permits assignment of a gene to one specific chromosome but not to a subregion. 

FDA. (1996). Points to Consider in Human Somatic Cell Therapy and Gene Therapy. 

FDA (1996) Addendum to the points to consider in human somatic cell and gene cell therapy, Human Gene Therapy 1 1181-1190. 

Currently, more than 400 human somatic cell gene therapy protocols are being tested. Most of these involve the use of genetically modified cells to treat noninherited diseases. For example, normal copies of the p53 tumor suppressor gene are inserted into lung tumors to halt tumor progression, and genetically modified cells have been used to create new coronary vessels in patients with coronary heart disease. Success has also been achieved in the treatment of hereditary disease (most notably, the recent successful treatment of X-linked severe combined immune deficiency see Clinical Correlate). 

Waldman T, Lee C, Nishanian TG, et al (2003) Human somatic cell gene targeting. Curr Protoc Mol Biol Chapter 9, unit 9.15... 

Rago C, Vogelstein B, Bunz F (2007) Genetic knockouts and knockins in human somatic cells. Nat Protoc 2 2734-2746... 

Eukaryotes A yeast cell, one of the simplest eukaryotes, has 2.6 times more DNA in its genome than an E. coli cell (Table 24-2). Cells of Drosophila, the fruit fly used in classical genetic studies, contain more than 35 times as much DNA as E. coli cells, and human cells have almost 700 times as much. The cells of many plants and amphibians contain even more. The genetic material of eukaryotic cells is apportioned into chromosomes, the diploid (2n) number depending on the species (Table 24-2). A human somatic cell, for example, has 46 chro-... 

FIGURE 24-5 Eukaryotic chromosomes, (a) A pair of linked and condensed sister chromatids from a human chromosome. Eukaryotic chromosomes are in this state after replication and at metaphase during mitosis, (b) A complete set of chromosomes from a leukocyte from one of the authors. There are 46 chromosomes in every normal human somatic cell. 

CBER (1998). Guidance for human somatic cell therapy and gene therapy. Hum. Gene Ther. 9, 1513-1524. 

Cell-based vaccines EMEA points to consider on the manufacture and quality control of human somatic cell therapy medicinal products 2001... 

Guidance for Reviewers Instructions and Template for Chemistry, Manufacturing, and Control (CMC) Reviewers of Human Somatic Cell Therapy Investigational New Drug Applications (INDs) (draft guidance) (August 2003)... 

Application of Current Statutory Authority to Human Somatic Cell Therapy Products and Gene Therapy Products. Federal Register 1993 58(197) 53248-51. 

Human somatic cells contain 46 chromosomes, cattle 60. and fruit fly 8. Thus, the diploid number bears no relationship to the species positions in the phylogenetic scheme of classification. 

Figure 19.2 A human somatic cell contains two sets of homologous chromosomes, which may be divided into two types autosomes and sex chromosomes. Autosomes are further divided into seven groups A-G. During the metaphase of cell division, each chromosome has been duplicated. Therefore, this karyotype consists of 92 chromosomes.

Telomeres are nucleoprotein structures located at the ends of eucaryotic chromosomes. They protect chromosome ends from fusion and degradation and ensure complete replication of chromosomal DNA. In human somatic cells, telomeres have 1.000 to 3,000 repeats. They gradually shorten with every cell division. This shortening i.s thought to limit their proliferative capacity. Cancer cells, in contrast, can maintain their telomere length and thus become immortalized. They do this by reactivating telomerase, a specific reverse transcriptase with an endogenous RNA template. ... 

Kim J et al (2008) An extended transcriptional network for pluripotency of embryonic stem cells. Cell 132(6) 1049-1061 Yu J et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858) 1917-1920... 

Carey BW et al (2009) Reprogramming of murine and human somatic cells using a single polycistronic vector. Proc Natl Acad Sci U S A 106(1) 157-162... 

Anokye-Danso F et al (2011) Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 8(4) 376-388... 

As often happens in these days of the human genome project, the human version hTERT) was found shortly thereafter [16, 17]. It was expressed in a variety of transformed cells but not detectable in primary cultures of human somatic cells, already giving a simple answer as to why telomerase activity was deficient in somatic cells. Thus, over a short time span, we went from having no telomerase protein to a whole family of TERTs (Telomerase Reverse Transcriptases). 

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... 

Human Somatic Cell Nuclear Transfer (SCNT)... 

Human Somatic Cell Nuclear Tranter (SCNT) 271... 

Human Somatic Cel Nuclear Transfer (SCNT) 273 Table 11.1 Conditions for human somatic cell nuclear transfer... 

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