Improvement in technology and biological approaches to modify human embryonic stem cells is gradually showing signs of advancement. A new and more efficient method is used to genetically alter human embryonic stem cells. This technique uses bacterial artificial chromosomes to substitute imperfect genes. It is likely that this advancement can be set as a stem cell development model that can be used to address human genetic diseases as well to treat other pathologies.
Professor of Biology at the University of California, San Diego, Yang Xu, said that this progress will help to broaden the field of human embryonic stem cells. Previously, any appropriate techniques to study and evaluate genetics were not available. This was well described in the January 8 issue, Journal Cell Stem Cell, by Xu and his fellow researchers, Hoseok Song and Sun-Ku chung.
Earlier methodologies used to modify genetics have all shown critical inadequacy. Xu team used BACs (bacterial artificial chromosomes) to considerably progress in the field.
BACs can be fused with human DNA and the bacteria does afterward replicate whereby the replications are congruent to the native genes of the chromosomes. There are BACs, which are commercially available and can be used to modify certain genes. The altered BACs that are induced to the human cells can switch segment of DNA or match up segment of human chromosomes. This matching process is called “homologous recombination”.
This approach is better as it can modify long sequences of genes in contrast to earlier techniques. This increases the likelihood that BAC will align with native DNA sequences. Using this advanced genetic modification of human embryonic stem cells method the team was able to alter and treat 20 percent of cells. Conventional method does usually only achieve a genetic modification capacity of 1 percent of the cells according to Xu.
The research team was able to introduce an imperfect copy of gene p53 in the human embryonic stem cell line. P53 is a suppressor of cancer. Moreover, during the second round of introducing p53 both lines of genes were disrupted.
Similar results were achieved with another type of gene, ATM. This gene can produce Ataxia-telangiectasia. It is a disease defined by hosting defections into various systems and it can thereby produce degenerative effects to brain cells, shortening telomeres and cancer.
According to Xu, to study shortening of telomeres it has to be done on human cells. Genetically engineered mice with for instance defective copies of ATM have some commonalities with human patients but not perfect similarities. The telomeres don’t shorten and neurons do not degenerate for mice yet for human it does.
The fact that experiment can now be conducted on human cell lines as a replacement mice can give clearer evidence. The actual experiment has already proven that ATM-deficient embryonic stem cell lines cause telomeres to shorten.
The research team said that many other experiments could be conducted similarly. They have already changed human genes with different stem cell lines. In the beginning, cell line that populated new colonies from unique cells was used but now the same has been done for a H9 cell lines. It is a cell line considered highly complex to alter.
The federal government is now funding research in H9 cell lines. Findings in genetic modification are already showing particular value. Eventually, this research was funded by California Institute for Regenerative Medicine.
Reference: ScienceDaily
Sat, Jan 9, 2010
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