Human cells from skin or blood can be reprogrammed to resemble the person’s embryonic stem cells and then cultured to generate cells specific to any part of that person’s body.

In the future, these patient-specific human induced pluripotent stem cells (iPSCs) could eliminate the need for donor transplants.

For now, they present an exciting new paradigm for modelling human disease and for individualizing drug testing, according to Dr. Lior Gepstein, director of cardiology at Rambam Health Care Campus in Haifa and holder of the Sohnis Family Chair in Tissue Engineering and Regenerative Medicine.

By adapting a Nobel Prize-winning technique from Japan, Gepstein’s lab pioneered a method to grow a patient’s own heart cells from that patient’s iPSCs in just a few weeks.

“We can use these cells for several things,” says Gepstein, who was among the featured presenters at Rambam’s 2016 annual international “State of the Heart” and digital-health summit at the end of May.

“The most ambitious project is to take a cardiac patient’s cells, reprogram them and transplant them back to a patient’s diseased heart to regenerate its function,” he tells ISRAEL21c.

“The heart cannot regenerate itself. Any dead areas [following a heart attack] are replaced by scar tissue and cannot contract, which leads to heart failure, the biggest problem we are facing as cardiologists.”

Gepstein’s lab has been working for several years to overcome many hurdles from theory to practice. Now, he reports, human clinical trials are only four or five years away thanks to strides made in a strategic partnership among Rambam, the University Health Network of Toronto (Canada) and the Technion-Israel Institute of Technology, where Gepstein is a member of the Rappaport Faculty of Medicine and Research Institute.

“A lot of labs have followed our lead, and this is a good sign that it is of great interest,” he says. “We were the leaders in the emerging field of cardiac regenerative medicine, and in many aspects we are still the world leaders in this area.”

Generating pacemaker cells

At the summit, Gepstein reported on his lab’s other sci-fi-like advances with iPSCs: growing heart pacemaker cells; studying a living patient’s heart disease and finding the most effective drugs to treat it before ever touching the patient; and as a platform for pharmaceutical development.

Gepstein explains that as we age, our heart’s pacemaker cells can start malfunctioning. Instead of implanting an electronic pacemaker as cardiac surgeons do today, they could implant the patient’s own brand-new pacemaker cells generated from iPSCs.

Gepstein’s lab also is dabbling in optogenetics, attempting to build a light-induced pacemaker and/or defibrillator. This would regulate the heart’s electrical activity by introducing a light-sensitive protein derived from algae.

“People have been using this in neuroscience but we are the first to use it in the heart,” says Gepstein, who published a paper about this research inNature Biotechnology.

Disease in a dish

Obviously, doctors can’t take out a patient’s heart to study genetic mutations that cause life-threatening conditions such as cardiomyopathy (heart muscle disease) or inherited arrhythmogenic syndrome.

However, by taking the patient’s skin cells and reprogramming them as heart cells — whose DNA is identical to the diseased cells –- the genetics can be studied and drugs can be tested in the culture dish to find out which will work best for the specific patient.

Gepstein and his colleagues used this method to save the life of a young woman in 2011, and have since demonstrated the ability to study and test treatments for dozens of cardiac genetic diseases using “disease in a dish.”

Now a major internationally funded study at Rambam is furthering the goal of generating patient-specific models of heart disease and individualizing treatment for that disease.

“This also provides the pharmaceutical industry, for the first time, with disease models of heart cells that they can use to develop new drugs,” says Gepstein. “If you have a promising drug with possible adverse side effects on the heart, you can test it in a lab dish instead of in humans before spending billions on development. Right now we are trying to find collaborations with the pharma industry.”

Your heart in a hologram

The conference also included a presentation by Dr. Elchanan Bruckheimer, medical director of RealView Medical Holography in Yokneam.

“This completely new technology developed in Israel provides an online holographic 3D image of the heart,” says Rambam Health Care Campus Director General Dr. Rafi Beyar, who is a cardiologist and professor of biomedical engineering at the Technion.

“Using RealView imaging, you can see the heart in front of you and manipulate and measure it while you are doing surgery on the actual heart. This new technology will change the way heart surgery is performed.”

Established in 2008, RealView has completed its first human clinical trials in interventional cardiology, and now is finalizing the design in anticipation of producing its first commercial products for 3D medical imaging.

Digital health startup incubator

Beyar told ISRAEL21c that the medical center recently launched a new digital health startup incubator in partnership with IBM, multinational medical-device company Medtronic and Pitango Venture Capital.

“In the next 10 years, the incubator will fund and support 40 companies in digital health, and I’m sure cardiovascular health will be the focus of at least 50 percent of their activities,” Beyar tells ISRAEL21c.

“Worldwide, cardiovascular disease is really taking a major role because it is still the No. 1 cause of death in the Western world despite huge advancements in cardiac medicine.”

Gepstein adds that cardiovascular disease is a growing problem because of the sheer numbers of older adults and also, ironically, “because we’ve become really good at saving people after heart attacks. They are alive but they have chronic heart failure. So this will be a huge clinical burden in the coming years.”

In addition to better devices and better drugs to fight this phenomenon, many digital health initiatives are aimed at prevention and lifestyle changes, says Beyar.

Among the successful worldwide companies spun off by Rambam MedTech, the medical center’s technology-transfer company, are two cofounded by Beyar himself: Instent, sold to Medtronic in 1996; and Corindus Vascular Robotics, now based in Massachusetts.

“We have this entrepreneurial spirit in Haifa that takes ideas and turns them into companies,” he says. “Rambam works side by side with the Technion and therefore the connection between bioengineering and innovation is very strong.”

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