Malignant gliomas and lung cancers are extremely aggressive and among or the most frequent cancers in humans with short median survival for patients. It is thus of importance for public health to develop new treatments. Our goal is to use human mesenchymal stem cells (MSC) for cancer diagnostic by imaging and/or therapy. Our first objective is to demonstrate an efficient homing to the tumor of systematically injected MSC. Prior IV injection, MSC will be labeled with nanoparticles (NP). Their distribution in various orthotopic or metastatic tumors models will be addressed using multimodality in vivo molecular imaging, non invasive MRI and optical imaging.

NP are multifunctional molecules that could be used like tracers for diagnostic and like vector for remote activation and therapy. Because of their chemical composition, their large size and their ability to be loaded with multiple drugs and/or tracers, one single NP can be imaged with different modalities and, in the same time, can serve as a pro-drug one can activate using imaging-guided irradiation.

MSC developed in the “Cellular and tissular therapy laboratory” associated with Grenoble hospital can be efficiently labeled with nanoparticles. Among different cell sources, MSC derived from bone marrow offer the advantage of not originating from a tumor or modified source. We will use these MSC like vectors of NP after ex-vivo loading. Indeed, it is well established that these cells are not inducing immunological responses and have the capacity to engraft and survive for a long period of time in the target tissue. Using these MSC presents also other advantages as compared to other stem cells, including the fact that it has been proved that their systemic delivery is feasible and safe in clinical trials and that their use in humans do not raise major ethical issues.

This project’s objective is thus to clarify the homing and potential therapeutic activity of hMSC for lung and glioblastoma imaging and treatment. The final and long-term aim of this work will then be to use these hMSC loaded with pro-drug containing NP and to activate them using different beams (Near-infrared, high frequency or X-rays).