Gene Modification Provides Hope to Heart Failure Patients

There has been a big leap forward in medical research. Scientists have modified skin cells from patients with heart failure so that they develop into new heart muscle cells. The breakthrough is reported in the European Heart Journal. It describes the genetic reprogramming of a subject’s own skin cells into ‘pluripotent stem cells’ or PSCs. Because the donor is the same person as the recipient, the chances of cell rejection are hugely reduced.

Cells donated from ‘strangers can sometimes lead to complications when the host immune system fights against the new implanted cells. This new procedure is the first step on a very long road, probably 5 to 10 years, towards full clinical trials.

Damaged heart cells have previously been repaired using donated cells but heart muscle cells are much less common and there is the ever-present likelihood of rejection. This new advance builds upon an earlier breakthrough where PSCs cultivated after being taken from more youthful healthier patients were a good bases for heart muscle cells. Older patients with unhealthy hearts had not been used as skin cell donors previously. Nor had it been tested as to whether new heart cells would become one with existing heart muscle.

The lead researcher at Rambam Medical Center in haifa Israel said, “What is new and exciting about our research is that we have shown that it’s possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young – the equivalent to the stage of his heart cells when he was just born.”

The team took a small sample of living skin cells from just two subjects who have had heart attacks.

And genetically modified them with ‘transcription factors’ and added molecules of valporic acid to the nuclei of the cells. A further transcription factor called c-myc was deliberately excluded because it is known to cause cancer. This is essential because previous attempts at cell-gene modification had been ruined when cells grew out of control and mutated into tumors.

The PSCs built with this innovative methodology were just as good as a source of genuine heart muscle as those built from the younger and healthier subjects. The combination of modified and existing heart muscle cells were thriving effectively side by side with two days. “The tissue was behaving like a tiny microscopic cardiac tissue composed of approximately 1000 cells in each beating area,” said the report’s author.

It is hoped that the PSC derived heart muscle cells will not be rejected after transplantation into the patients from which they were sourced. This is now the main фокус of the team’s research. the next big obstacle is to make the transition from laboratory mice to human subjects. Currently mice are being given immunosuppressive drugs in order that the transplanted cells remain in place.

Further barriers to full clinical trials are; deriving a clinically significant number of derived cells, removing the risk of causing cancer, eliminating the dangers of interrupting the heart’s rhythm and finding an effective cell grafting strategy that helps them survive to maturity. No wonder clinical trials are five to ten years down the road.