Prof. Yosef Itzkovitz talks about his plans to produce insulin-secreting cells to cure diabetics and the revolution coming out of Stanford, where they succeeded in rejuvenating an old mouse
On the tenth floor of the Rappaport building in Haifa, adjacent to Rambam Hospital, there are three or four large containers on the floor. In them, in liquid nitrogen at a temperature of minus 190 degrees Celsius, is one of the preserved treasures of medicine and biotechnology in the world: embryonic stem cells, which serve as a basis for all research in their field.
In the next room is the laboratory of Prof. Yosef Itzkowitz, one of the few in the world who shares the patent for the creation of embryonic stem cells. In the laboratory there are hundreds of flasks, some in the process of sterilization on the way to serve as a habitat for new embryonic stem cells, and some in the refrigerator, in which you can observe the formation of the precious cells.
Embryonic stem cells are extracted six days after fertilization of the egg. Their aggregate size is about a tenth of a millimeter, and they include about 50 cells surrounded by an outer layer. In a normal pregnancy, a fetus develops from the cells, and from the outer layer a placenta develops. In the laboratory, development stops at this stage, and the cells are used for research.
The research use of cells is controversial in the world from a moral point of view, as some consider it to be infanticide. On the other hand, the enormous healing potential inherent in embryonic stem cells, in the eyes of many, qualifies their use for scientific purposes.
What is special about embryonic stem cells is that all body cells develop from them. Deciphering the process of their differentiation into specific cells - such as heart, blood, liver or nerve cells - fascinates researchers. Understanding the process of differentiation, for example into heart cells, could enable the development of a pool of heart cells that will wait on the shelf for transplantation in heart patients, to repair defects or as a replacement for a heart transplant.
Itzkowitz's laboratory is located in the Technion's center of excellence for stem cell research where about 20 researchers from the Technion, Rambam Hospital, the Faculty of Medicine and the Rapaport Institute. Itzkowitz, who holds a full-time position as director of Rambam's Department of Women and Maternity and IVF Unit, is also a member of the Rapaport Institute and a faculty member at the Technion.
At a relatively early stage, Itzkovitz teamed up with Professor Nissim Benvanishti from the Hebrew University of Jerusalem for further research. The collaboration yielded intellectual property at a relatively early stage of global research in the field.
"Recently it was decided on a new joint venture between the Technion and the Hebrew University for Research and Development, with the possibility of commercializing the findings," said Itzkovitz. "The goal of the project is to produce insulin-producing cells for transplantation in diabetic patients, and to produce liver cells as a model for testing the toxicity of substances and drugs," he added. The funding may come from the research and development programs of the European Union, which is also interested in the field.
The results of the research on insulin-producing pancreatic cells are encouraging, but the road to producing cells for transplantation is still very far, warns Itzkowitz. "We don't even have cells similar to pancreatic cells yet. What we have are cells that secrete insulin, which cannot be transplanted." The research is based on introducing genes that encourage insulin production into the fetal cells.
Another applied direction studied in the stem cell laboratory is the preparation of cells to form blood vessels, including heart cells, intended for transplantation. "For the first time in the world, pulsating muscle cells created in the laboratory were in my laboratory, at Michal Amit's," said Itzkovitz.
The great revolution of the stem cells will be when it will be possible to stop the aging process with them. Five years ago, when scientists talked about "stopping the biological clock", it seemed that this was still science fiction. Lately the idea has become less imaginative.
"Recently they proved something amazing", said Itzkowitz. "Research done at Stanford in California proved that embryonic stem cells can be rejuvenated in an adult mouse. The researchers took a young mouse and an old mouse and connected their blood systems. They saw that the exposure caused the old mouse's stem cells to regenerate, a process called grief. The search for substances that will rejuvenate our stem cells may be one of the biggest revolutions in medicine in our generation," he added.
"I see in the future the creation of drugs that will encourage the growth and rejuvenation of stem cells and allow the healing of organs and systems in the body, which will enable the healing of diseases, stopping the aging process or at least reaching an advanced stage of life in a better condition. In addition, it will be possible to use embryonic stem cells to cure chronic and acute diseases, when the cells will be on the shelf, ready to be transplanted into any person", estimated Itzkovitz.
According to him, the global race to decipher the secret of embryonic stem cells is already known in the US as "gold rush number 2". Itzkowitz said that after California announced the raising of 3 billion dollars for the field, academic institutions in other US states began allocating hundreds of millions of dollars to research on embryonic stem cells, fearing that researchers would move to California.
"The global competition is becoming tough because of the association of official academic bodies of countries with companies for the purpose of research development. That's why we also need to join forces. Our ambition is to reach cooperation at a national level and with parties abroad, because the research requires considerable investments", he added.
"Michal Amit produced the first lines of embryonic stem cells"
The global breakthrough in embryonic stem cell research in the late 90s gave Israel and Prof. Itzkovitz a competitive advantage. "In '98, we produced embryonic stem cells in a laboratory at the University of Wisconsin in Madison, USA," said Itzkovitz. Itzkowitz was a partner in Prof. James Thompson's research group, in which Michal Amit also participated, who continues to work with Itzkowitz in his laboratory. "She was the one who managed to produce the first lines of embryonic stem cells," he said.
The team led by Thompson succeeded in duplicating embryonic stem cells and preserving them under special conditions in the laboratory, so that they would continue to divide while maintaining their properties. "They can be grown forever, unlike an adult stem cell that dies at the end of its journey," said Itzkowitz. The patent for the process was registered in Wisconsin, and the Israeli partners received cells for research use in Israel and rights to use the technology.
"The collaboration with Wisconsin allowed me to establish the first laboratory in the world outside the USA, in collaboration between Rambam and the Technion," said Itzkovitz. Since the cells she produced in Wisconsin were created before 2001 - when the American legislation became stricter with those involved in the field - Itzkowitz was able to receive funding for research from American federal institutions. "We received 2.5 million dollars. We are funded for three years and a discussion is currently underway on funding for another three years."
By: Ora Koren, Haaretz, Walla News!
