Technion scientist uses stem cells to heal broken hearts, spines
Nowhere is the magic conjured by innovators greater than in medical technology.
By SHLOMO MAITAL
For more than 40 years, I have studied innovation and creativity as an economist at the Technion. Living in a “house by the side of the road,” I have the privilege of researching dozens of brilliant faculty members and graduates, as they race, walk and stumble down the start-up road. And, I confess, more than once I wished I could actually leave that roadside dwelling and walk and run with them.Lately, with a friend and colleague, I’ve been interviewing 100 leading Technion innovators, for a book whose title captures the essence of entrepreneurship: Aspiration, Inspiration, Perspiration. (Never underestimate perspiration). During these interviews, I keep hearing the words of science fiction writer Arthur C. Clarke: “Truly advanced technology is indistinguishable from magic.”Nowhere is the magic conjured by innovators greater than in medical technology. Here is the story of one such magical breakthrough – the pioneering research on tissue engineering of Prof. Shulamit Levenberg, dean of the Faculty of Biomedical Engineering, and her discovery of how to use stem cells to heal broken hearts and repair damaged spinal cords.Levenberg earned her PhD at the Weizmann Institute. She then did her post-doctoral research in tissue engineering at MIT, in the legendary lab of Prof. Robert Langer. In a pioneering article with Langer, she wrote that “the clinical goals of tissue engineering are to restore, repair or replace damaged or lost tissues in the body.”Her breakthrough discoveries involve in-vitro vascularization (blood vessel formation) of engineered tissues. When stem-cell tissues are implanted, the engineered vessels anastomose [i.e. connect] with the host’s blood vessels, improving survival and functioning of engineered grafts. In other words, the implant’s blood vessels link up with the body’s existing blood vessels in the damaged organ, and the resulting blood supply nurtures them and helps them thrive.What sparked Levenberg’s interest in tissue engineering? She recalls meeting Prof. Judah Folkman when he lectured at the Weizmann Institute on development of an anti-cancer drug based on blocking blood vessel activity. Folkman was the youngest full professor in the history of Harvard Medical School. He showed how cancer tumors attract blood vessels in order to grow and spread and helped develop drugs that prevent this.That meeting and a newspaper story about the new field of organ engineering ignited her desire to understand how human tissue is organized.She told the business daily Globes: “Folkman researched how tissue creates a network of blood vessels for itself that gives it the amount of blood flow precisely adjusted to the size of the tissue and optimally spreads around all of the tissue. This mechanism really excited me. I told myself, ‘I’d like to understand how this is done, so that I can imitate it.’ Sometimes one sentence spoken by one person influences the direction of another person’s life. That’s how I started dealing with tissue engineering, with an emphasis on blood vessels. I left biology for medical engineering, which is multidisciplinary.”Many scientists have worked on using stem cells to repair ailing organs. Levenberg realized early that such “scaffolding” was imperfect unless a way could be found to feed the cells with an adequate blood supply. She was the first to engineer vascularized tissue flaps, offering novel reconstruction techniques using engineered tissue constructs. With colleagues, she has shown how ailing hearts could be mended in this way.
She recently developed unique stem-cell engineered tissue constructs that induce the regeneration and repair of injured spinal cords, and showed such regeneration in rats. Immobile rats, owing to spinal cord trauma, were enabled to walk again. The implications for the disabled are enormous – in the US, for example, there are over five million people who suffer from paralysis, and for over a quarter of them, the cause is spinal cord injury.Last year, she told Globes: “I have hope that we can really help people walk again. I heard Yariv Bash, the entrepreneur of Beresheet [a Israeli robotic lunar lander that in April 2019 crashed just yards before landing safely on the moon], who was paralyzed in an accident, ask, ‘Why can people bring a spaceship to the moon, but can’t repair two centimeters in the spinal column?’ and I said to myself, ‘We’re starting. We’re in the right direction.’ The rats are walking, although there’s a long way to go before we get to people, of course.”The Report: Please tell us about the key milestones in your life.Levenberg: “I grew up in Zichron Ya’acov, at the time a rural and intimate place. During my National Service I was a guide for the Society for the Protection of Nature. Then I became interested in biomedical engineering, but at the time there were no undergraduate studies in this topic, thus I studied biology; in 1999 Technion was the first to open Biomedical Engineering undergraduate program in Israel and since then has the largest and most impactful BME program in Israel.“I took my BA degree at the Hebrew University and did PhD studies at the Weizmann Institute. Then I proceeded to a postdoc in tissue engineering at the Robert Langer Lab at MIT. At the time, this was a revolutionary domain and it attracted me due to the potential to heal people and save lives. When I returned to Israel – I enjoyed Technion support in establishing a well-equipped lab to continue my research and development in the domain.“Currently, a group of 20 graduate students, post-docs and researchers work in the lab and advance our solutions as we go! I am proud of the many students that graduated from my lab and went on to senior positions in industry as well as academics, at Technion and other institutes.“For the past four years I served as dean of the biomedical engineering faculty. This was quite challenging – to maintain my research work, maintain family life (I have six lovely children) and advance the achievements of the faculty. We grew the faculty to 21 academic staff, 170 students per cohort in the undergraduate program and a growing diversity of domains and collaborations with new joint programs with other faculties such as physics and the medical school. We encourage our students to pursue practical projects that may be applied in the medical and commercial domains. I am proud of our faculty and believe it is the best demonstration of multi-disciplinary studies: engineering, science and medical. It should be expanded further!“What do you regard as your most important innovation or creative idea?“It goes without saying that the foremost breakthrough that I led is in the tissue engineering domain. This is an on-going adventure during the past 20 years, from the early postdoc research through on-going improvements and new findings. For instance, recently, we demonstrated the ability to cure spinal defects to the point of enabling rats that were fully paralyzed to become able to walk! We hope this could be proven in humans in the coming years!“What advice would you give to the young generation of students?“Focus on what you enjoy doing and on what is important for society and humanity – this will lead to satisfaction and nurture success. The biomedical engineering domain bears such wonderful potential! Do not hesitate to pursue directions that are unique!“IT IS often not easy to persuade scientists to agree to publicity. Levenberg agreed, because she strongly believes her Biomedical Engineering Faculty should be greatly expanded. Biomedical technology is already a leading global growth industry and it could potentially be enormously important for Israel’s future.The global pandemic has accelerated technological change in healthcare. According to the business weekly The Economist, citing a McKinsey report, “global digital-health revenues – from telemedicine, online pharmacies, wearable devices and so on – will rise from $350 billion last year to $600b. in 2024. The groundwork for what looks poised to be the next trillion-dollar business has been accelerated by the pandemic. Money is pouring in.”Pouring in, alas, everywhere – except by the Israeli government. A report by my S. Neaman Institute colleagues, Tsipy Buchnik, Rinat Klein and Dr. Daphne Getz, on medical research in Israel reveals that investment in hospital research has declined by 20% in the past five years; a long-term strategy for healthcare is nonexistent; and only 0.5% of government R&D spending go to medical research.The report’s subtitle says it all: “The Government Must Wake Up Before the Next Crisis.” Fruitful partnerships between creative Israeli doctors and imaginative scientists have led to amazing breakthroughs in the past. Growing numbers of medical students are opting for joint programs that combine MD studies with science and engineering degrees.But biomedical research and the start-up ventures that result from it need resources. Will Science and Technology Minister Izhar Shay, a successful entrepreneur and venture capitalist, wake up the government and lead the way?■The writer heads the Zvi Griliches Research Data Center at S. Neaman Institute, Technion and blogs at www.timnovate.wordpress.com