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Therapeutic potential of iPS cells may be limited by reprogramming errors and genomic instability

January 24, 2016

Here's how ICSP cells work. Researchers use a viral vector to introduce a gene called v-Myc into neural progenitor cells. Myc, one of four standard genes already used to generate iPS cells, triggers self-renewal, guiding cells through the replication process. Scientists are sometimes cautious when it comes to adding genes like Myc - if cells keep dividing after transplantation in a patient, cancer could develop - but v-Myc is known to be safer than other flavors of Myc. What's more, the v-Myc used here is conditionally expressed. This means that ICSP cells can only produce v-Myc when the researchers add a compound called tetracycline to laboratory cultures. When tetracycline is removed, the cells cease dividing and start differentiating. Then, once transplanted into to an animal model, ICSP cells are no longer exposed to tetracycline and take their growth and differentiation cues from their new environment.

In this study, ICSP cells differentiated into active neurons and other brain cell types with therapeutic payoff for an adult rat model of intracerebral hemorrhagic stroke - the rodents show improved behavioral performance. Although the long-term genomic stability of ICSP cells remains to be seen, no adverse effects have arisen over five months of observation. The team envisions that this ICSP approach will also extend to progenitor cells obtained from other organs, such as heart, pancreas, or muscle, potentially accelerating the use of stem cell therapies for a broad range of diseases.

Source: Sanford-Burnham Medical Research Institute