Heart Damage in Mice Repaired With iPS Cells
Circulation, July 20, 2009
Researchers at the Mayo Clinic in Rochester, Minnesota, have used induced pluripotent stem (iPS) cells to treat damaged cardiac tissue in a mouse model of heart attack. The iPS cells were found to repair the heart tissue both structurally and functionally.
According to Timothy Nelson, M.D., Ph.D., one of the lead investigators of the research, "This study establishes the real potential for using iPS cells in cardiac treatment. Bioengineered fibroblasts acquired the capacity to repair and regenerate infarcted hearts."
Previously, iPS cells had been tested in animal models for three other diseases, namely, Parkinson's disease, sickle cell anemia, and hemophilia A. This new study is the first of its kind in which iPS cells were tested specifically for their ability to regenerate cardiac tissue.
As Dr. Nelson further explains, "We're taking advantage of a diseased tissue environment that is sending out a distress signal that is asking the tissue to repair itself. When we put these iPS cells in, they are able to respond. They were able to respond to this damaged environment and spontaneously give rise to the appropriate tissues and create new tissues within that diseased heart. That is a key 'wow factor' of this paper. It was obvious to the observer which animals had been treated and which ones hadn't."
The scientists used fibroblasts which they genetically reprogrammed to dedifferentiate into iPS cells which were then redifferentiated into heart tissue. When transplanted directly into the damaged hearts of the mice, the new cells were found to have engrafted within two weeks of transplantation, and by 4 weeks the transplanted cells were found to have contributed to improved structure and function of the hearts. Not only did the iPS cells halt the progression of structural damage within the heart muscle itself, but the iPS cells were also found to regenerate new cardiac tissue which included not only heart muscle but also blood vessels. Ultrasound also revealed significant improvement in the ability of the hearts to pump blood.
According to Adre Terzic, M.D., Ph.D., Mayo Clinic physician and senior author of the study, "This iPS innovation lays the groundwork for translational applications. Through advances in nuclear programming, we should be able to reverse the fate of adult cells and customize 'on demand' cardiovascular regenerative medicine."
However, the researchers still used dangerous viral vectors for dedifferentiation of the fibroblasts into iPS cells, even though other scientists have replaced such methods with less dangerous reprogramming techniques.
Nevertheless, according to Dr. Nelson, he believes that iPS technology will be able to be used in clinical therapies to help people, eventually, even though it might take "several years". Until then, iPS cells are still ineligible for clinical therapeutic use since there are still a number of biological hurdles remaining that have yet to be overcome.
Meanwhile, autologous adult stem cells have already been used therapeutically in the clinical treatment of heart and other conditions, and are already available in clinics around the world - except, that is, in the U.S., where outdated FDA regulations have been unable to keep pace with scientific progress.