Scientists Claim Fix To Stem Cell Immune Rejection Problem

Date (2015-08-21 )

Last year, check Japanese researchers announced that the first human patient would be treated with induced pluripotent stem cells in an attempt to reverse a degenerative eye condition called macular degeneration that leads to vision loss.

Now, discount a team of scientists headed by biologists at UC San Diego has discovered how induced pluripotent stem (iPS) cells, ampoule which are derived from an individual’s own cells, could be programmed to avoid rejection from the immune system.

Their findings, published online ahead of print in the journal Cell Stem Cell, show that iPS cells can differentiate or change into various types of functional cells with different fates of immune rejection. The authors say it is the first study to evaluate these cells’ immunogenicity – their ability to provoke an immune response and the degree to which it provokes a response.

“With the new findings, we cannot assume anymore that all cells derived from patient-specific iPS cells will be immune-tolerated by the patient,” said Yang Xu, a biology professor at UC San Diego who headed up the research, in an interview.

First produced from mouse cells in 2006, iPS cells have generated immense enthusiasm for their potential to treat a wide range of diseases without the ethical and political concerns that come with human embryonic stem cells. The original reprogramming method to make iPS cells uses viruses to introduce key genetic material that prompts cells into an immature, embyronic-like state. The breakthrough earned Japanese inventor Shinya Yamanaka at Kyoto University a Nobel Prize.

Unlike embryonic stem cells, iPS cells are derived from an individual’s own cells, so the thought has been that these cells will probably avoid rejection by the immune system. But Xu and his colleagues discovered in 2011 that, despite this, the abnormal gene expression can cause the immune system to reject certain cells derived from iPS cells. Another safety concern with iPS cells is that, in some cases, they have caused tumors in animals treated with these therapies instead of spurring the growth of healthy tissue.

For this latest study, the researchers developed a variety of cell types from human iPS cells then tested them in humanized mice, which are designed to have an immune system that mimics a human’s. Xu and his team found that that smooth muscle cells derived from iPS cells were highly immunogenic, or strongly rejected by the immune systems of the humanized mice, while retinal pigment epithelial cells – destined for the eye – were well tolerated by the immune system.

This is promising news for iPS cell-based therapies to treat macular degeneration, a major cause of blindness and visual impairment in older adults. Macular degeneration affects an estimated 30 million to 50 million people worldwide.

The stem cell field has a lot hinging on the Japanese clinical trial testing iPS cells, which started in September 2014. If successful, the trial would provide evidence of the clinical potential of iPS cells and pave the way for more human trials.

Earlier this month, New Scientist reported that the Japanese trial has been halted after genetic mutations were detected in the cells of the second trial participant. The first subject to receive an experimental iPS cell treatment, a 70-year-old woman, is reportedly healthy.

The new findings from the UC San Diego team could help researchers better understand which iPS-cell therapies will have more favorable outcomes in patients, possibly reducing the risk associated with these treatments.

Still, Xu acknowledges that there is yet another hurdle to overcome for the stem cell therapy to be successful. “Macular degeneration-associated inflammation can also kill cells transplanted into the lesion,” Xu said. “This would be another immune-related challenge for iPS cell-based therapy.”

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