Name: Frederick Lang High School: St. John’s School, Houston, TX Mentor: Dr. Anwar Hossain

1. Name: Frederick Lang High School: St. John’s School, Houston, TX Mentor: Dr. Anwar Hossain Project Title: Human Bone Marrow Mesenchymal Stem Cells as Biofactories for Exosomes Containing Anti-Glioblastoma miRNA Treatment of Glioblastoma Multiforme (GBM), the most malignant adult brain tumor, is limited because of the unique biology of GBMs, including the presence of Glioma Stem Cells (GSCs), and because the blood brain barrier prevents efficient delivery of most therapies. To overcome these hurdles, I tested a novel strategy using human bone marrow mesenchymal stem cells (hMSCs), which home to GBMs, as “bio-factories” for producing exosomes carrying anti-glioma miRs. I show that miR-124 can inhibit the growth of GSCs, identifying miR-124 as a new agent to target GSCs. Then, in Transwell experiments designed to mimic delivering hMSCs carrying miR-124 to patients with GBMs, I show, for the first time, that hMSCs engineered to overexpress miR-124 inhibit the growth of GSCs. Finally, I show, also for the first time, that hMSCs can package miR-124 into exosomes and that these exosomes can be isolated from the supernatant of hMSCs and delivered to GSCs, inhibiting GSC growth, in experiments designed to mimic delivering mir-124-exosomes to patients with GBMs. These studies provide the first proof that hMSCs can be used as either intra-tumoral or ex vivo “biofactories” for miR-124-exosomes, setting the stage for in vivo studies and ultimately for translation to patients with GBM.