Frankenstein, baby's heartbeat solve medical challenge
It鈥檚 an electrifying step forward for cardiac research: a new method of maturing human heart cells that simulates their natural growth environment while applying electrical pulses to mimic a fetal heart rate.
The discovery, which offers cardiac researchers a fast and reliable way to create mature human cardiac patches in a range of sizes, was announced by University of Toronto researchers in the scientific journal Nature Methods.
鈥淵ou cannot obtain human cardiomyocytes (heart cells) from human patients,鈥 explained Milica Radisic, Canada Research Chair in Functional Cardiovascular Tissue Engineering and Associate Professor with the Institute of Biomaterials and Biomedical Engineering and the Department of Chemical Engineering & Applied Chemistry.
Because human heart cells鈥攊ntegral for studying the efficacy of cardiac drugs, for instance鈥攄o not naturally proliferate in large numbers, researchers have been using heart cells derived from reprogrammed human induced pluripotent stem cells (hiPSC鈥檚), which tend to be too immature to use effectively in research or transplantation.
鈥淭he question is: if you want to test drugs or treat adult patients, do you want to use cells that look like and function like fetal cardiomyocytes?鈥 asked Radisic, who was named a 鈥淭op Innovator Under 35鈥 by MIT Technology Review and more recently was awarded the Order of Ontario and the Young Engineers of Canada 2012 Achievement Award.
鈥淐an we mature these cells to become more like adult cells?鈥
In response to the challenge, Radisic and her team, which includes graduate student Jason Miklas and Dr. Sara Nunes, a scientist at the University Health Network (UHN) in Toronto, created a 鈥榖iowire' where human heart cells derived from stem cells are seeded along a silk suture typical to medical applications.
The suture allows the cells to grow along its length, close to their natural growth pattern.
Like a scene from Frankenstein, the cells are then treated to cycles of electric pulses which have been shown to stimulate the cells to increase in size, connect and beat like a real heart tissue.
But the key to successfully and rapidly maturing the cells turns out to be the way the pulses are applied.
Mimicking the conditions that occur naturally in fetal cardiac development鈥攚hen the heart rate escalates before birth, the team ramped up the rate at which the cells were being stimulated, from zero to 180 and then 360 beats per minute.
鈥淲e found that pushing the cells to their limits over the course of a week derived the best effect,鈥 said Radisic.
Grown on sutures that can be sewn directly into a patient, the biowires are designed to be fully transplantable. The use of biodegradable sutures, important in surgical patches that will remain in the body, is also a viable option.
The research has practical implications for health care, said Miklas.
鈥淲ith this discovery we can reduce costs on the health care system by creating more accurate drug screening.鈥
The development takes cardiac research one step closer to viable cardiac patches, said Nunes, a cardiac and a vascularization specialist.
鈥淥ne of the greatest challenges of transplanting these patches is getting the cells to survive, and for that they need the blood vessels," Nunes said. "Our next challenge is to put the vascularization together with cardiac cells.鈥
Radisic, who calls the new method a 鈥済ame changer,鈥 is quick to point out just how far the field has come in a very short time.
鈥淚n 2006 science saw the first derivation of induced pluripotent stem cells from mice,鈥 she said. 鈥淣ow we can turn stem cells into cardiac cells and make relatively mature tissue from human samples, without ethical concerns.鈥
(The paper, "Biowire: a platform for maturation of human pluripotent stem cell鈥揹erived cardiomyocytes," can be found at .)
Erin Vollick is a writer with 茄子直播's Institute of Biomaterials and Biomedical Engineering.