Prof. András Dinnyés is a leading researcher of embryology, cloning, and stem cell biology both in Hungary and worldwide. As the speaker of the December edition of the Alumni Hungary Webinar Season, he held a fantastic presentation on genetic reprogramming and DNA revolution. We interviewed him on this highly interesting field which truly brings a new shift for medicine.
What does genetic reprogramming mean? Why is this field considered a new paradigm in medicine?
Genetic reprogramming or more accurately epigenetic reprogramming allows changing the information on the selection of genes active in a given differentiated cell type which was set during development. The resetting of the cell type-specific information into a more open status, equivalent to that of stem cells in a newly fertilized embryo generates the possibility for birth of new animals from such reprogrammed cells, or multiplication of the stem cells and subsequent differentiation into very different somatic cell types. These later options allow the use of such cells for regenerative medicine which is a paradigm shift compared to traditional small molecule-based treatments.
BioTalentum, the company you founded, among others, also works on a European Union project regarding the treatment of type 1 diabetes. What are the latest results of this research? When do you think diabetes can be cured?
We are using genetically reprogrammed human pluripotent stem cells as the source of differentiation into beta-cells, the cell type which is destroyed in type1 diabetes in the patient’s body. By replacing the insulin-producing cells by transplanting them in a protective device, we can not only restore the biological insulin/sugar-control mechanisms but also avoid the often deadly long-term side effects of diabetes. Our own studies are showing excellent success in mouse cell transplantation studies with 3D pancreatic beta-cell spheroids, and some international companies also moved into the first human clinical trial stages with similar approaches. This herald a new era of regenerative solutions for chronic diseases.
The widespread of cloning and stem cell treatment in therapy is a very slow process. What factors, legislative changes could facilitate this process?
The regulators, the researchers and companies developing the new therapies are all learning about the new cell-based methods, which are very different from traditional legislation and quality/safety control needed for chemical drugs. The European Commission and EMA published a joint action plan on such advanced technology medicinal products (ATMPs) in 2017, which aims to streamline procedures and better address the specific requirements of ATMP legislation. The positive intention is clearly there, and EMA provides consultation in all stages of the ATMP development, yet still very few permits have been issued. With every positive story of a newly approved cell therapy, we hope that the system will be streamlined. Unfortunately, there are also rogue clinics selling unproven and unauthorised treatments for a huge profit for vulnerable patients – thus there is a continuous struggle by the regulators to control such illegal activities, at the same time.
There are ongoing researches on the usage of animal organs transplanted in human for the treatment of severe diseases. How this method could help? Do you think our society is ready to accept such treatments?
There is a serious shortage of transplantable donated human organs, thus many patients die on the waiting lists. Organs from animals, for example, pigs would provide a good remedy, however, the animals need to be genetically modified to avoid rejection by the human immune system. Such pigs have been generated already, and in monkey experiments, xenotransplanted pig hearts, kidneys, livers, pancreatic islets survived for prolonged periods. We expect that human clinical trials can start in the near future, as life-saving therapies would be considered ethically acceptable and very much demanded by the affected patient groups.
How do you see the future of genetic reprogramming? Where is this field developing, what are the prospects for the near future?
The legacy of the first adult cell reprogramming in mammalians resulting in the birth of Dolly, the cloned sheep in 1996 exist in the form of applications in endangered species preservation efforts for example in rhinos and jungle cats, and also applied in pet, horse and bull breeding. The transgenic pigs for xenotransplantation and for large animal models of human diseases have been created mostly by nuclear transfer cloning. The human induced pluripotent stem cell technology has an even bigger importance, as a major source for in vitro disease modelling and toxicology assays. These methods are going to change the way we test drugs, chemicals without the use of live animals. The most important outcome, however, might be the regenerative medicine applications, in 3-10 years they will be available in clinics all over the World.
