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Download the Stem Cell Guide for Life Science Researchers
:: Posted by American Biotechnologist on 08-07-2011
Stem cell scientists, do not despair! Despite concerns over iPSC-derived teratomas and altered genomic and epigenomic states, researchers at UC Davis have written a roadmap for finding solutions to the problems identified with iPSCs which has been published last week in the journal Cell.
According to Paul S. Knoepfler, UC Davis associate professor of cell biology and human anatomy:
iPSCs offer the potential to treat many diseases as an alternative or adjuvant therapy to drugs or surgery. Problems that have been identified with their use likely can be overcome, allowing iPSCs to jump from the laboratory dish to patients who could benefit from them.
:: Posted by American Biotechnologist on 07-25-2011
Stem cell researchers at UCLA have generated the first genome-wide mapping of a DNA modification called 5-hydroxymethylcytosine (5hmC) in embryonic stem cells, and discovered that it is predominantly found in genes that are turned on, or active.
According to Steven E. Jacobsen, a professor of molecular, cell and developmental biology in the Life Sciences and a Howard Hughes Medical Institute investigator, 5hmC is formed from the DNA base cytosine by adding a methyl group and then a hydroxy group. The molecule is important in epigenetics because the newly formed hydroxymethyl group on the cytosine can potentially switch a gene on and off.
The molecule 5hmC was only recently discovered, and its function has not been clearly understood, Jacobsen said. Until now, researchers didn’t know where 5hmC was located within the genome.
:: Posted by American Biotechnologist on 04-05-2011
Scientists from the Morgridge Institute for Research, the University of Wisconsin-Madison, the University of California and the WiCell Research Institute moved gene therapy one step closer to clinical reality by determining that the process of correcting a genetic defect does not substantially increase the number of potentially cancer-causing mutations in induced pluripotent stem cells.
Their work, published in the online edition of the journal Proceedings of the National Academy of Sciences and funded by a Wynn-Gund Translational Award from the Foundation Fighting Blindness, suggests that human induced pluripotent stem cells (iPS) altered to correct a genetic defect may be cultured into subsequent generations of cells that remain free of the initial disease.
However, although the gene correction itself does not increase the instability or the number of observed mutations in the cells, the study reinforced other recent findings that induced pluripotent stem cells themselves carry a significant number of genetic mutations.
In brief, scientists produced iPS cells by episomal reprogramming, corrected a disease-causing mutation by homologous recombination and removed the puromycin cassette that was used for gene selection using Cre recombinase.
Results of the study indicate that both homozygous recombination and cassette removal did not increase the iPS mutational load. Nonetheless, the initial induction of primary dermal fibroblasts into iPS cells lead to a fairly substantial mutational load at the time of derivation.
This study is important in that it demonstrated that downstream cloning events do not introduce further mutations into iPS cells which can be a source of tremendous therapeutic value. Nonetheless, it is important for further studies to focus on reducing mutational events caused by iPS induction which may be a serious drawback to introducing iPS therapy into the clinic.
:: Posted by American Biotechnologist on 06-29-2010
A recent study published in the New England Journal of Medicine reported that autologous limbal stem cells can be used to permanently reverse the loss of vision caused by ocular burn induced limbal stem-cell deficiency (limbal stem cells function to replace dead corneal cells).
It is important to note that in the cases reported, eyesight damage was caused by neovascularization, chronic inflammation, and stromal scarring which resulted in an added epithelial layer that either blurred or caused total loss of vision. Furthermore, since the healthy stem cells used in the culture and subsequent transplant were obtained from the second, healthy eye, the reported therapy is only effective in patients with a remaining healthy eye.
The methodology involved culturing a biopsy of the patient’s contralateral eye co-cultured with irradiated 3T3-J2 feeder cells which were then transplanted into the damaged eye.
82 out of 107 eyes that had undergone treatment exhibited fully restored eyesight, which was for the most part stable throughout 10 years of follow up.
Unfortunately the study is being used as a political tool by some camps to discredit the use of human Embryonic Stem Cells for medical research. The claim of some in the pro-life camp is that since the study used adult stem cells (induced pluripotent stem cells) it is “proof” that the human embryonic stem cell debate is dead and that induced pluripotent stem cell therapy can provide just as effective (if not more effective) results. (For a great primer on the difference between embronic stem cells and pluripotent stem cells see Stem Cell Basics for Life Science Researchers).
Whatever the case may be, this is a very elegant study with fantastic results to be celebrated by all.
Rama, P., Matuska, S., Paganoni, G., Spinelli, A., De Luca, M., & Pellegrini, G. (2010). Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration New England Journal of Medicine DOI: 10.1056/NEJMoa0905955