INTERVIEW: The Future of Mesenchymal Cells Therapy

Meet Prof. Dr. Miomir Knežević, professor at the University of Ljubljana and a founder of several biotech companies.

Miomir Kneževič

Image courtesy TSmedia, medijske vsebine in storitve, d.o.o.




“Stem cells offer new opportunities for better quality of life and also better survival of the patients.”






KLEMEN: Hello Splice, I am here with Prof. Dr. Miomir Knežević. He is a professor at the University of Ljubljana and also a founder of several biotech companies. One of the companies he founded many years ago is called Educell and it’s working with bringing stem cell therapies to clinic. Since last year you started treating Graft-versus-Host Disease (GvHD) using mesenchymal stem cells and you have some really amazing successes with patients. You saved couple of lives. Could you tell a little bit about the stories with your patients?

MIOMIR: Hello Splice! Recently we started to treat new type of diseases with stem cell therapies. The number one or the leading cell type which is used now are so called mesenchymal stem cells. This type of stem cells are found in our bone marrow and other body parts which acts as a master cell bank. And then in each tissue you have so called working cell banks which are repairing the damage that has been done. One of the functions of these cells is not only regeneration of the tissues but more prevention of inflammation, like a peace-keeper in the body. And they are also working trans-person so they could be also used as autologous or allogeneic product. They are not showing any side effects. One of these diseases as you mentioned is a fatal disease called Graft-versus-Host Disease. We see it in 60% of all allogeneic transplants of bone marrow. But side effect of such a transplantation is that donor cells are attacking hosts tissue because they recognize it as an enemy and they are provoking very strong reactions especially on the skin and in the gut. Such a disease in the mild form can be easily controlled by immunosuppression with different types of biological antithymocyte therapies but in some cases, this is in 20% to 30% of cases, the form of GvHD is so strong that these classical therapies are not working. So, recently it was shown that infusion of mesenchymal stem cells control or correct such a disease and it works immediately. Basically you take a bone marrow aspirate of the donor, cultivate these cells, multiply them several hundred times, store them in liquid nitrogen and then in the fractions infuse them into the patient. 

Working with stem cells

Image courtesy Educell d.o.o.

KLEMEN: Is there any special treatment that you do to these cells once they are taken from the donor?

MIOMIR: We have to select the cells which are attaching to the plastic surface and we check which markers they are expressing and these are the classical mesenchymal stem cell markers. Now the scientific society is still discussing how these cells work. We know that they are a factory of growth factors and they can have a very potent immunomodulatory effect but the end mechanism is not known. Unfortunately for this treatment the same rules apply as if you would test a classical drug. And to test a drug there are certain rules and clinical trials which should be performed according to the good clinical practice. However, standards for cell therapies are different to those of classical drugs. Namely the main requirements from the pharmaceutical agencies is that the drug is sterile. It is obvious that this type of drug is different and if somebody would expect that we will prepare products according to the legislation as it is now, such an approach would have nothing to do with common sense.

KLEMEN: I’ve heard the story how you saved the life of the boy. I think it was your first patient. Can you tell the story again?

MIOMIR: It happened last year in July, when we got a report from the pediatric clinic from Prof. Jazbec. He asked us for help, because they had a patient who was in a terrible stage of GvHD, but he was a great fighter and he was putting all his efforts to survive. It was a boy of 18 years old. Before he was in full power. He has had three types of cell transplantation and the third one was successful, but it provoked this strong negative response as a GvHD. So, he lost 40 kg and he was supposed to die in few days. At the end of August we immediately took donation of the bone marrow of his father. Our team immediately cultivated the cells and in the middle of September he got the first dose and later he got two other doses. The first reaction was seen a few days after application. The strongest success was seen after one month. And this was really dramatic. The boy was before already one year in the hospital and after the therapy he was supposed to go to the rehabilitation and he went home for Christmas. However, the immunosuppressive therapies he received were so strong that he got a very strong infection, pneumonia and sepsis, which at the end finished his life. We were all very sad because he was really willing to live. You can read the full story on Splice. Despite this stem cells offer new opportunities for better quality of life and of course also better survival of the patients. New patients will be also adult patients. For them we have to prepare higher number of mesenchymal stem cells to treat them.

Mesenchymal stem cellsKLEMEN: Mesenchymal stem cell therapy for GvHD is now in experimental phase. Obviously the results are very promising. So, if everything goes according to the plan, when will this kind of treatment become regular treatment for everybody with the need for bone marrow transplantation?

MIOMIR: I see this in the next few years, because when you have such a powerful weapon which really works, you are obliged to use the short cuts. Because you cannot just in the name of science or rules take the opportunity, it is unethical to take the opportunity to the patients to be a part of new powerful therapy. So, for the cases when it is obvious that classical standard therapy is not working, it will be used immediately. And these cases will be included in these trials, it won’t be just case by case. But optimization of the treatment after the classical bone marrow transplantation will take several years, since we have to be sure that taking off the strong immunosuppressant or reduce the amount of it can also cause a side effect of a very strong GvHD which most probably cannot be controlled by mesenchymal stem cells, as it is an experimental therapy and is quite expensive. But later on, if it is used on the standard basis, it will be acceptable also from the socio-economic point-of-view.

KLEMEN: Thank you Miomir, you are doing wonderful things, good luck!

MIOMIR: Thank you Klemen and all the best to all of you!




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