STEM CELLS, GENE THERAPY AND MAGNETIC NANOPARTICLES - TRIPLE COMBINATION USED IN FIGHT AGAINST CANCER
A new approach to anti-tumour therapy was published on October 27, 2017 in the International Journal of Nanomedicine. Members of the multidisciplinary team were also prof. Melánia Babincová and prof. Peter Babinec from the Faculty of Mathematics, Physics and Informatics of Comenius University in Bratislava.
By: Peter Babinec
Thanks to more timely diagnosis and progress in tumour therapy, the survival of oncology patients in some types of tumours is still improving. However, some solid tumours, such as pancreatic tumours, brain tumours, and advanced metastatic tumours of the stomach, lung and esophagus, cannot be cured by standard therapy. The median of survival of these patients is not improving and is extremely small. The reason for the low efficacy of standard therapy is the low directness of these drugs to tumour cells, the emergence of tumour resistance to chemotherapy, and the undesirable toxic side effects on the patient. Further advances in the treatment of aggressive tumours and metastases require principally new therapeutic approaches.
In our body we have mesenchymal stem cells that are responsible for the repair of damaged tissues. It has been found that they can migrate in the body, find a place of harm in the body, come to it and regenerate it. The tumours also perceive also as a damage in need of repair. They can therefore be used as a means of transport that would bring something to the tumour to destroy it. "Antitumour therapy must be directed only to tumour cells and act intracellularly to lead to cure," says the lead author, the prominent Slovak oncologist prof. Čestmír Altaner, DSc., whose group already 12 years ago as a first in the world, developed suicidal gene therapy directed to the tumour site by mesenchymal stem cells. Genetic modification of these cells by a gene transforms the non-toxic drug into an effective cytotoxic agent only at the site of the tumour, causing no undesirable side effects.
Tumour tropism of mesenchymal stem cells was also an inspiration for labelling these cells with magnetic nanoparticles to be used for very sensitive MRI diagnostics and for magnetic field-induced hyperthermia. The possibility of therapeutic use of high frequency magnetic field and functional magnetic nanostructures for controllable release of drugs and simultaneously for hyperthermia of tumours was proposed by prof. M. Babincová, DSc. in her study already in 1993.
Further progress has been made in this project when we have found that therapeutic stem cells are secreting exosomes into the medium in which they are grown and that in a cargo of these exosomes is preserved mRNA of a suicidal gene. This means that the so called therapeutically conditioned media can be used to kill tumour cells. Even more surprising was the finding that such cells labelled with magnetic nanoparticles produce larger exosomes that contain these nanoparticles in a high concentration. Thus, we have created a hybrid magnetic nanosystem directed to tumour cells. Numerous samples of various human tumour cells affected by magnetic nanostructures obtained from therapeutic stem cells under the influence of an alternating magnetic field have shown that this way the tumour cells can be heated to 43 oC in 10 minutes causing their death. Nanostructures produced by mesenchymal stem cells have the advantage of being directed to tumour cells, are natural, non-toxic, thus constitute an innovative drug. Future experiments on animal models will be a further step closer to their use in patients with severely treatable oncological diseases. However, there is a need for funding that is lacking.
The published work is an illustration of the need for cooperation between seemingly differently oriented scientific institutions, such as the Oncological Institute of St. Elizabeth, Institute of Experimental Oncology BMC, SAV, Faculty of Medicine and Faculty of Mathematics, Physics and Informatics of Comenius University in Bratislava, to realize new ideas leading to important discoveries that can help sick people.
U. Altanerová, M. Babincová, P. Babinec, K. Benejová, J. Jakubechová, V. Altanerová, M. Zdurienčíková, V. Repiská, and Č. Altaner: Human mesenchymal stem cell iron oxide exosomes for magnetic-hyperthermia targeted to tumour cells, International Journal of Nanomedicine 2017:12;7923–7936