Theracell is in the process of developing novel therapies for the treatment of cancer. These therapies make use of Adipose-Derived Stem Cells (ADSCs) and a special class of nanoparticles, referred to as Superparamagnetic Iron Oxide Nanoparticles (SPIONs). These particles exhibit the phenomenon of “superparamagnetism”, i.e., on application of an external magnetic field, they become magnetized and on removal of the magnetic field, they no longer exhibit any residual magnetic interaction.
Stem cells (MSCs) can be an important tool for the treatment of cancer. It has been shown, that, once injected intravenously, mesenchymal stem cells (MSCs), acquired either from bone marrow or from adipose tissue, migrate toward and distribute within distant tumor foci. In other words they show a tumor tropism. MSCs can home specifically to tumors including gliomas, breast, colon, ovarian, and lung carcinomas, among many other primary and metastatic tumors. In these models, MSCs have successfully homed to tumors from a large variety of administration routes including the carotid artery, femur, tibia, and trachea.
MSC tumor migration is motivated by many factors, including tumor cell-specific receptors and soluble tumor-derived factors such as stromal cell-derived factor-1, tumor necrosis factor (TNF)-a, and interleukins, among other identified and unidentified inflammatory mediators. Therefore, in the context of tumor tropism, MSCs represent an excellent tool as cellular vehicle for local delivery of antitumor agents.
The delivery of drugs into the tumor remains however an issue when the stem cell model is used for the treatment of cancer. Once the cells reach the malignancy, they must release the therapeutic agent locally. Also, the delivery of these drugs must take place only within the tumor, so that other, healthy cells remain unaffected. To date there is no such an approach that exploits a) the use of stem cells for the transfer of therapeutic agents in human tumors and b) the manipulation of stem cells for the selective release of these agents directly into the malignancy.
The combination of super paramagnetic iron oxide nanoparticles (SPIONs) with Adipose-Derived Stem Cells (ADSCs) is an innovative project currently developed by Theracell, with the aim to end up with the production of a powerful Cytonanotechnology platform for the effective treatment of cancer. The principle is based on a three-step mechanism, is the following:
- Through an internally developed technology, SPIONs are effectively internalized by ADSCs. Special care is being given to create superparamagnetic stem cell constructs, without affecting the viability and functionality of the cells. Therefore the choice of the right SPION is of the utmost importance.
- Two additional nanoparticles are also constructed: one containing an antitumor drug (i.e. doxorubicin) and another one containing a telomerase inhibitor. These two nanoparticles are also transferred into the cells, in parallel with the SPIONs.
- After the cells have been loaded with the three types of nanoparticles, they are injected intravenously. They are then attracted to the tumor by applying an external magnetic field. The majority of the cells is attracted at the site of the malignancy.
- By alternating the magnetic field at a specific frequency, the SPIONs within the cells start to vibrate. This vibration increases the temperature at 42-45oC, which is a temperature that human cells cannot tolerate. As a result most of the tumor cells die. Due to the fact that the stem cell-SPION complexes are mainly located within the tumor, the surrounding tissue remains unaffected. Therefore, the tumor is selectively targeted even if the field is applied over a relatively large volume of tissue. This effect is referred to as “Magnetic Fluid Hyperthermia”.
- At the same time, during the application of the alternating magnetic field, the stem cells also break up and they release the antitumor compound as well as the telomerase inhibitor. The antitumor drug “kills” the cancer cells that have evaded cell-death related to the effect of the Magnetic Fluid Hyperthermia.
- It is well known that, in comparison with normal cells, cancer cells express a higher level of telomerase. The release of a telomerase inhibitor, which is also released at the tumor site, blocks the telomerase activity of the malignant cells, which become senescent and die.