An interview with Prof. Lior Gapstein on the occasion of his winning the Bruno Prize
There is (nothing) more whole than a broken heart, said Rebbe Makotsek and beautifully composed Naomi Shemer, but in practice it is probably not the case.
Myocardial tissue has a limited regenerative capacity, therefore any damage to the myocardial cells during a myocardial infarction is irreversible and may lead to the development of heart failure. Heart failure syndrome is responsible for more hospitalizations than all cancers combined. says Prof. Lior Gepstein, a researcher at the Technion School of Medicine and an active cardiologist at the Rambam Medical Center. According to him, about half of the patients suffering from heart failure die within five years, and quite a few require a heart transplant, an organ that is obviously in constant shortage. In the Laboratory for Cardiac Electrophysiology and Regenerative Medicine headed by Prof. Gepstein, a number of researchers as well as outstanding students are working on a variety of solutions, different from each other, but all with one goal - to enable the restoration of damaged tissues through integration into the revolution of the last decade - the stem cell revolution and tissue engineering.
Stem cells have two main properties: the ability to divide and create stem cells identical to the original and on the other hand the ability to differentiate into different types of mature cells. In the adult there is a pool of stem cells in many tissues. These cells are responsible for the constant regeneration of tissues such as skin tissue, as well as for the creation of various blood cells. However, the differentiation ability of these cells is relatively limited and they cannot differentiate into a wide variety of cells. In Prof. Gepstein's laboratory, they study the differentiation capacity of a special type of stem cells: human embryonic stem cells. The origin of these stem cells is in the primary cells that develop in the embryo, when at the age of three days it is in a state known as a blastocyst - a kind of ball whose shell will eventually become the placenta, and from its face ("the inner layer of cells") all the organs of the embryo will develop. In 1999, a group of researchers led by Prof. Jamie Thompson from the University of Wisconsin and in collaboration with Prof. Yossi Itzkovitz from the Technion succeeded in isolating the "inner layer of cells" from a number of blastocysts and creating from them the first human embryonic stem cell lines.
In other laboratories they are trying to turn the embryonic stem cells into liver, pancreas and other cells. In Prof. Gepstein's laboratory, they are trying to turn as many of them as possible into heart muscle cells. "These cells are a unique research tool that allows us to shed light on the signaling pathways associated with heart development. In addition, the human heart tissue created in the laboratory allows us to study how the heart will react to new drugs before they are used in clinical trials on humans. However, the main long-term goal of the laboratory is to create new heart cells that will allow in the future to replace those that died during a myocardial infarction and thus improve the function of the failing heart."
"I started research as soon as I heard from Prof. Itzkovich about the development of embryonic stem cells and within a short time we were able to grow human heart cells for the first time in the laboratory. In this work, which was a significant breakthrough, we also showed that the resulting muscle cells are characterized by all the characteristic properties of heart cells. They contained genes and proteins unique to heart cells, in the electron microscope we saw that they had the structure of heart cells, a characteristic electrical activity was recorded in them, and they beat faster in the presence of adrenaline."
"The next question we examined was whether we could use the resulting heart cells to repair the cardiac damage following a heart attack. To this end, we conducted extensive experiments in tissue cultures as well as in a model of myocardial infarction in rats. In these experiments, we showed that the transplanted heart cells knew how to synchronize with the existing heart tissue and even cause a significant improvement in heart function compared to rats in which stem cells were not transplanted."
However, the obstacles facing the clinical application of stem cell technology are still numerous. It is very difficult to "convince" the stem cells to become heart cells, and it will certainly be a problem when we want to produce millions of cells for the purpose of healing. Another problem is the expected immune rejection following the transplantation of these cells. A unique solution to the latter problem is found in the discovery of a Japanese scientist named Yamanaka who succeeded in reprogramming mature skin cells and giving them the properties of embryonic stem cells. Today, this unique technology of creating induced stem cells is also used in Prof. Gepstein's laboratory and recently succeeded in this way in leading to the creation of heart cells from the skin cells of subjects. The vision is that a person who needs to undergo cardiac rehabilitation will come to the clinic, they will take skin samples from him, create stem cells from them and transplant them according to the need and the nature of the injury. In the shorter term, this ability will make it possible to create research models of genetic diseases in the laboratory that we currently do not have the opportunity to study.
Prof. Gepstein estimates that even in five years he will be in the same position. "Perhaps in a decade we will begin to see clinical trials of these technologies and another decade until they become practical. However, already in the early stages we will be able to use the stem cell technology for additional applications."
"My background as a research doctor, who deals with both cardiology and basic research, is quite a rare animal in Israel. The advantage of this is the possibility to ask questions that come from my daily life as a doctor. When a clinical problem arises that has no solution, the tools of basic research can be used to understand it better, and find solutions. In the USA, the field is very developed and it promotes both science and medicine there. Unfortunately, the doctor-researcher model is very neglected in Israel mainly due to the lack of resources and regret.
At the level of Israeli society, we must change the priorities and invest in education from elementary to universities so that the children's role models are scientists and not celebrities. Also, one should be careful about the bias of the budgets from basic to applied research, because the future of the country depends on basic research.
About
Prof. Lior Gepstein is an associate professor in the Department of Physiology and Biophysics, Faculty of Medicine, Technion - Israel Institute of Technology. He received at the Technion a Doctor of Medicine degree in 1996, and a Doctor of Philosophy degree in 1999. After a period of post-doctoral research at the University of California, San Francisco (then he also won a Rothschild scholarship) he returned to the Technion and founded the Laboratory for Cardiac Electrophysiology and Regenerative Medicine .
Interviews with the four winners were published in a special booklet published in honor The award ceremony
