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Prof. Michel Rebel at the Life Sciences Baltics 2012 conference: "Stem cells can be used to restore the pancreatic islets of diabetic patients"

Prof. Rebel is the chief scientist of the startup company Kadima Stem in the Science Park at the Weizmann Institute

Prof. Michel Rebel at the Life Sciences Baltics 2012 conference. Photo: Avi Blizovsky
Prof. Michel Rebel at the Life Sciences Baltics 2012 conference. Photo: Avi Blizovsky

Stem cells were the topic of the main scientific panel within the Life Sciences Baltics 2012 conference that took place last week in Vilnius, Lithuania, in the presence of about 120 Israelis among the 700 participants. Prior to that, the plenary session of the conference was held and the main lecture of the second day (the one of the first day was given by the Nobel laureate Prof. Ada Yonat) was delivered by Prof. Michel Rebel from the Weizmann Institute.

Although Prof. Rebel retired from the institute, today he is the chief scientist of the startup company Kadima Stem. "The company was founded at the end of 2009. Today we employ 25 people in the science park of the Weizmann Institute, and have a thousand square meters of laboratories. The company's goal is to develop industrial medical applications of embryonic stem cells and to a certain extent induced cells (induced stem cells can differentiate into any tissue in the body like embryonic stem cells and unlike other adult stem cells).

We do not produce the cells from fertilized eggs or embryos ourselves but work with licenses. Among other things, we have a license from Hadassit (the implementation company of the Hadassah Medical Center) to use the cells produced by Prof. Benjamin Rubinoff. These are fetal stem cells at a clinical level that were produced under GMP conditions - according to FDA instructions, without the use of animal materials to develop the cells (the stem cell itself is of human origin, of course).

Due to the fact that these are induced cells, these cells or their derivatives could be used in human experiments. We have two main programs: one in the field of diabetes and the other in the field of multiple sclerosis. In the field of diabetes, we produce pancreatic islet cells from these cells, which produce the insulin and glucagon whose role is to regulate the amount of glucose in the blood. As we know, in type 1 diabetics these cells are destroyed by the immune system and in type 2 diabetes these cells do not function properly due to excess weight, age and so on. 40% of patients with type 2 diabetes need insulin, which means the cells do not produce enough insulin, in the other 60% of patients there is enough insulin, but the problem lies elsewhere."
"Our idea is to provide pancreatic cells that have matured in vitro in a process that takes 3 weeks. The cells produce insulin and glucagon and they respond to glucose by producing more insulin when the blood glucose level rises. They are functioning well but right now we need to make the process industrial on a large scale. It will take time.
And what about the transplant itself, is it safe, will the cells continue to work even inside the body?
Prof. Rebel: "For some reason it takes a lot of time from the transplant until there is good control over the amount of sugar in the blood. As for the transplantation process itself, there is little experience because it is already carried out today, albeit with the contribution of Ai Labalev from cadavers. The problem is that the amount is currently sufficient for the 0.1% of patients who can benefit from it. It takes brain death and more than one body but it works. Therefore, our method will make it possible to produce a product in industrial production that can help thousands and tens of thousands of patients. From my experience, I always give the example of Interfarm. When we started with 5 milliliters of interferon beta, we peaked at 175 liters. Today, the material is produced in a factory near Lake Geneva and stored in facilities with a capacity of 30 liters. If the drug works, it is possible to increase the output required to reach production, and then not 0.1% of the patients will receive a response, but all of them and at a good price."

The second project that occupies about half of Kadima Stem's resources is in the field of drug scanning. The idea is to develop from the stem cells human tissue that is very difficult to obtain otherwise in order to search for new drugs. In our case, we developed a patented process that allows us to produce cells that are normally found in the brain and spine and produce the myelin sheaths - called oligodendrocyte cells

"We can reproduce in vitro the formation of myelin if we mix these cells with nerve cells and then we see the formation of a myelin sheath and observe it with the help of antibodies. We then use a commercial image processing system (Silomix) that provides us with the analysis of many groups of cells, in 96 wells at the same time. You can try 96 substances or different concentrations of 10 substances and thus find new drugs that speed up the myelin production process.
The currently accepted drugs for multiple sclerosis, including Rebif (which sells Serono ointment) and Avonx (the drug sold by the Israeli Biogen for which the Weizmann Institute receives royalties) and of course Copaxone work to slow down the destruction of myelin by the immune system.
Today, pharmaceutical companies are looking for substances that, instead of slowing down the destruction, will increase the repair, and this is the goal of the scan we are doing with the Merck-Serono company, which signed a five-year contract with us in April of this year. They send to Israel materials that have shown some initial activity and ask us to prove that it works on human cells, which is our uniqueness (others work with mouse cells). They also tell us what the concentration of each substance is so that we can evaluate which concentration is more effective. After locating what the active substance is, the chemists process several thousand substances from it again and we test them for them."

In response to a question from the audience as to whether the ethical issue will not stop the development of the application of stem cells, Prof. Rebel answered: "I have been involved in the bioethics of embryonic stem cells since 2000 in the Bioethics Committee of UNESCO."

"Many countries have decided not to allow the use of surplus embryos from treatments to create stem cells. I think this is a mistake. There is a lot of unused fertilized eggs. The parents can donate these eggs for medical research. There is no other use if they do not want more children, these eggs have no reproductive potential and the other alternative is to keep them frozen forever. In many countries it has been decided to allow parents to donate under ethical control these eggs to produce embryonic stem cells. I don't think it had any effect on the research. In the US it was illegal to use federal money during the Bush era. Obama confirmed. There are countries like Germany and Norway that have completely banned the use."

In any case, there is international cooperation, there is a registry of cells that researchers can receive and the opportunities are open. In addition, there is a new field called induced stem cells, which is a developing field and may reduce the importance of embryonic stem cells, and will be an alternative to them."

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