Milica Radisic and her team recently announced in the scientific journal, Nature Methods, that they have developed a new method of maturing human heart cells by applying electrical pulses to the cells, in a pattern that mimics the fetal cardiac development of humans. The new technology, called ‘Biowire’ uses silk sutures to grow human heart cells which are mature enough to be used in research and transplantation. Electrical pulse is applied to the cardiomyocytes that mimics the fetal heart rate of humans to stimulate a natural environment for the heart cells to mature in. This new process has achieved much better results than previous methods to mature stem cells derived from human caridomyocytes.
Radisic, who is the Canada Research Chair in Functional Cardiovascular Tissue Engineering, was named a “Top Innovator under 35” by MIT Technology Review and has received the Order of Ontario and the Young Engineers of Canada 2012 Achievement Award. Her team included Dr. Sara Nunes, a scientist and cardiac and vascularization specialist at the University Health Network (UHN) Toronto, and Jason Miklas, a graduate student at the University of Toronto.
The problem faced by cardiovascular researchers is that human heart cells are not good at multiplying naturally and so researchers have to use reprogrammed human induced pluripotent stem cells. However, the problem with using hiPSC’s is that they do not mature properly and so are not very effective in research and transplantation. These cells are used to test the effectiveness of cardiac drugs but the results can be misleading when the tests are carried out on immature cells. It is known that these fetal cardiac cells don’t fare well when used to treat adult patients.
Radisic and her team found the solution to the problem of maturing these cells by applying cycles of mild electrical pulses to mature them. The trick was to mimic the natural patterns of increasing heart rate that occur during cardiac biological development of the human fetus. By slowly increasing the rate from 0 to 180 and then to 360 beats per minute, they were able to stimulate the natural growth environment for the cardiomyocytes. The result was that the cells grew along the length of the suture, matured and connected with each other and started beating like a real human heart tissue. Using a suture also helped the cells grow in a way similar to their natural growth pattern and hence the name of ‘Biowire’. The team also found that pushing the cells to their limits over a period of a week delivered the best results.
The potential benefits of this new technology can be huge and Radisic is positive that it will turn out to be a ‘game changer’ in the field of cardiac research. Now it is possible to make relatively mature cardiac tissue from human samples without any ethical concerns. New drugs can be tested on mature heart cells which will result in better medicines and accurate drug screening. This will eventually help in lowering the costs on the health care system. These ‘Biowires’ can be grown quickly and easily in a variety of different sizes depending on the requirement of the researcher. As they are grown on silk sutures they can be used directly for sewing into the patient’s heart and are designed to be fully transplantable. Biodegradable sutures can also be used and this adds to the practicality of the ‘Biowire’.
Radisic, who is also an associate professor at the Institute of Bio-materials and Bio-medical Engineering (IBBME) and the Department of Chemical Engineering at the University of Toronto, feels that the field of cardiac research has grown by leaps and bounds in a very short time. Only 7 years ago in 2006, the first derivation of pluripotent stem cells from mice was seen. Now, thanks to Radisic and her team, it has become possible to convert stem cells into cardiac cells and to mature them into transplantable heart tissue.
There are still improvements to be made in this field. The next step is the development of viable cardiac patches which would require the vascularization of the mature cardiac cells because only with the development of blood vessels will these cardiac patches be able to survive after transplantation. However, despite all the work still required to be done, this new technology is definitely a big step forward for cardiac research.