About This ProjectOur laboratory is searching for the next generation of brain cancer treatments by modifying stem cells harvested from human fat. We modify these fat stem cells to release a therapeutic molecule, BMP4, which has been shown to suppress GBM growth. With your help, we can get closer to developing a personalized brain cancer therapy that utilizes the stem cell’s present in a patient’s own fat.
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What is the context of this research?
Glioblastoma (GBM) is the most common primary intracranial cancer in adults with a median survival time of about 14 months after diagnosis. The dismal prognosis is due to the limited effect of current therapies, and a small hypothetical group of stem cells, called brain tumor initiating cells (BTICs), that is responsible for tumor recurrance. Our team has found that stem cells from a patient’s own fat may have the potential to deliver new treatments directly to the brain. Mesenchymal stem cells (MSCs) have a natural ability to migrate towards cancerous tissue. Bone morphogenetic protein (BMP4) has been shown to suppress brain cancer and specifically have an effect on BTICs. MSCs could be harnessed as carriers of therapeutic molecules, such as BMP4, against brain tumors.
What is the significance of this project?
The heterogeneous makeup of brain tumors makes it near impossible to destroy with current therapies. Mesenchymal stem cells isolated from human fat tissue have the potential to act as a “smart device” that tracks migrating brain tumor cells. This incredible ability can be harnessed by modifying these mesenchymal stem cells to release a therapeutic molecule. In this project, the therapeutic molecule is BMP4, which has been shown to make brain tumor cells grow less, migrate less, and even differentiate. Additionally, mesenchymal stem cells open the door to personalized medicine. Patients can donate their own fat tissue, where researchers can then harvest the mesenchymal stem cells, modify them, and then use the mesenchymal stem cells to fight their own brain tumor.
What are the goals of the project?
1. Collect adipose tissue and brain tumor tissue samples from patients. Harvesting MSCs from fat is less invasive and expensive than harvesting stem cells from bone marrow.
2. Harvest mesenchymal stem cells from patient-donated adipose tissue and modify them to secrete BMP4. Bone morphogenetic protein 4 has been shown to decrease proliferation and drive BTIC differentiation. Therefore, adipose-derived MSCs engineered to secrete BMP4 (hAMSCs-BMP4) may be a potential effective treatment option for GBM.
3. Test the effect of these modified mesenchymal stem cells (hAMSCs-BMP4) on the patients’ brain tumor in vitro, specifically assessing tumor growth, differentiation, and migration.
Isolating and growing MSCs from human fat requires a specific, expensive media. The requested funds will buy a supply of this media, as well as reagents to make more BMP4 virus to modify the fat tissue, and a specific assay to test the migration of GBM cells.
Meet the Team
Dr. Alfredo Quiñones -Hinojosa received his undergraduate from UC Berkeley and earned his medical degree from Harvard with Honors. He did his residency at the University of California San Francisco, and currently works at Johns Hopkins in Baltimore, Maryland. His titles include Professor of Neurological Surgery, Professor of Oncology, Director of the Brain Tumor Surgery Program at Johns Hopkins Bayview Medical Center, and Director of the Pituitary Surgery Program at Johns Hopkins Hospital. Dr. Q also oversees two labs in his efforts to discover the ability of stem cells to fight brain cancer.
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Press and MediaPlease watch this video that features dr.Q speaking about the lab and the progress that is being done to find a cure for brain cancer. https://www.youtube.com/watch?v=MzJ8k46HQ0M
"Using fat to fight brain caner."
"The biggest challenge in brain cancer is the migration of cancer cells. Even when we remove the tumor, some of the cells have already slipped away and are causing damage somewhere else," says Dr. Quinones-Hinojosa. ”Building off our findings, we may be able to find a way to arm a patient’s own healthy cells with the treatment needed to chase down those cancer cells and destroy them. It’s truly personalized medicine.”
As quoted in the press release, “ideally, [Dr. Quinones-Hinojosa] says, if MSCs work, a patient with a glioblastoma would have some adipose tissue (fat) removed – from any number of locations in the body – a short time before surgery. The MSCs in the fat would be drawn out and manipulated in the lab to carry drugs or other treatments. Then, after surgeons removed the brain tumor, they could deposit these treatment-armed cells into the brain in the hopes that they would seek out and destroy the cancer cells.”
Additional InformationThe following is from a young husband and father, Andrew, who was one of the 24,620 people diagnosed with brain cancer this year and Dr. Quinones-Hinojosa's patient. His story highlights the importance of finding better treatment options.
"Just when I thought things in my life were falling perfectly into place, I was thrown a curve ball when I least expected it. I was happily married to my wife, Allison, with two beautiful kids ages 4 and 1 1/2, we had recently bought a house in D.C., and I had a wonderful job as a political fundraiser. All in all, I'd say life was great, but suddenly my whole world came crashing down when, at the age of 36, I was diagnosed with an oligodendroglioma astrocytoma mixed glioma Grade III. I had so many emotions running through my mind when I found out that I had a cancerous brain tumor. I was shocked. I was scared; I thought, why me, why now? But once my wife and I got over the initial shock, I knew I was going to do everything in my power to fight this cancer. If cancer wants to pick a fight with me, I am not going to back down and let the cancer win; I'm determined to beat cancer. I know the odds may not always be in my favor, and there are going to be times when I feel defeated, but that's when I find the strength to fight even harder. There may not be a cure for my brain tumor now, but I believe one day I will be able to tell my children I am cancer-free."
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