Research Abstract
Successful treatment of CNS pathologies remains one of the greatest challenges. The recognition that different stem cell types, including mesenchymal and neural stem cells, can integrate appropriately throughout the mammalian brain following transplantation has unveiled new possibilities for their use in transplantation. Our laboratory has shown that different stem cell types home to sites of cerebral pathology and thus can be armed with therapeutic transgenes, a strategy that can be used to inhibit tumor growth by targeting angiogenesis or selectively induce apoptosis in proliferating tumor cells in the brain.
Our research is based on developing clinically translatable models of both primary, recurrent and metastatic brain tumors, and stem cell based cell surface receptor therapeutics that simultaneously target cell death and proliferation pathways in an effort to eradicate brain tumors. We have engineered different stem cells types to release therapeutic proteins to specifically induce apoptosis in tumor cells and anti-angiogenic to inhibit tumor angiogenesis and tested them in primary and metastatic mouse tumor models. In recent years our laboratory has also focused on targeting tumors that are resistant to different therapeutic drugs and oncolytic viruses. Resultantly, we have developed stem cell deliverable bi-modal therapeutic molecules and oncolytic herpes virus and shown their efficacy in mouse models of aggressive and invasive brain tumors. Very recently, we have created different immunomodulatory stem cells to boost tumor resection induced CD4/8 T cells post-tumor debulking and shown therapeutic efficacy in different mouse tumor models. Inherently linked to the brain tumor therapy paradigm are imaging techniques, thus we employ fluorescent/bioluminescent imaging markers and optical imaging techniques to track stem cells, image apoptosis and changes in tumor volumes in real time in vivo.
In an effort to translate stem cell based therapies into clinical settings, we have shown that encapsulation of receptor targeted stem cells in synthetic extracellular matrix prevents their rapid “wash- out” post-transplantation in the tumor resection cavity and has a significant therapeutic benefit on the survival of mice bearing resected brain tumors. Our research program is committed to achieving the vision of creating an “off-the-shelf” therapeutic offering for cancer that would positively impact the quality of life of individuals affected across the globe.
