Ability To Track Stem Cells In Tumors Could Advance Cancer Treatments

"Stem cell cancer therapies are still in the early stages of development, but they offer great promise in delivering personalized medicine that will fight disease at the cellular level," said Hui Wang, a postdoctoral fellow from Prof. Xiaoyuan (Shawn) Chen's group of the Molecular Imaging Program at Stanford (MIPS), Department of Radiology at Stanford University, Stanford, Calif., and lead researcher of the study, Trafficking the Fate of Mesenchymal Stem Cells In Vivo.

"Our results indicate that molecular imaging can play a critical role in understanding and improving the process of how stem cells migrate to cancer cells. Eventually, this technique could also be used to determine if gene-modified stem cells are effective in fighting cancer."

MSCs are adult stem cells that have the ability to transform into many different types of cells, such as bone, fat or cartilage. Many scientists believe that stem cells show great promise in treating different types of diseases--and a few stem cell therapies are already used to fight some types of cancer. Leukemia patients who haven't responded to chemotherapy, for example, may receive bone marrow transplants, through which stem cells of a healthy bone marrow donor are injected into the patient's blood stream.

If the transplant is successful, the stem cells will migrate to the patient's bone marrow and begin producing healthy cells that will replace the cancer cells. For other types of cancer, researchers are experimenting with modifying stem cells that could be engineered to deliver chemotherapy more precisely to specific tumor sites.

For these types of treatments to be successful, the ability to track what happens to stem cells after they are injected into a living organism is essential. Currently, three different tracking techniques are used: radiolabeling, which consists of using a radioactive substance to tag the cells; magnetic labeling, or using magnetic nanoparticles to tag cells for magnetic resonance imaging; and reporter-gene tracking, which involves engineering genes that can adhere to cells and be tracked with molecular imaging technologies. Of these, reporter gene techniques are highly sensitive and able to monitor cell migration, survival and proliferation over time in living organisms.

In their research, Wang and her team isolated stem cells from adult mice and engineered a reporter gene that would be both luminescent and green under a special microscope. Two tumor models were also tagged with reporter genes that were luminescent and red. The tumor cells were injected into live mice either intravenously or under the skin, followed days later by injection of the engineered stem cells.

The study produced solid evidence that the injected stem cells migrate to the tumors and don't begin to differentiate into other types of cells until they are at the tumor sites. In some of the mice, the breast cancer cells had begun to spread to the lungs. Researchers found that the injected stem cells also migrated to the lung cancer tumors. In addition, the stem cells that migrated to lung tumors differentiated into bone cells, while the stem cells that migrated to breast cancer tumors differentiated into fat cells. The results indicate that stem cells can migrate both to breast cancer cells and their lung metastasis. In addition, the MSCs differentiate into distinctly different cells. "The next logical step of this study is to incorporate therapeutic genes into MSCs and use multimodality molecular imaging techniques to follow the distribution, homing, survival, proliferation and cell/gene therapy efficacy of the MSC platform," said Wang.

Wang and her team will be presented with the SNM Molecular Imaging Center of Excellence (MICoE) Abstract Award for their work. The award will be presented during SNM's 55th Annual Meeting by MICoE President Martin Pomper, M.D., Ph.D.

Scientific Paper 106: H. Wang, F. Cao, A. De, S. Gambhir, J. Wu, and X. Chen, Department of Radiology, Stanford University, Stanford, Calif., "Trafficking the Fate of Mesenchymal Stem Cells In Vivo," SNM's 55th Annual Meeting, June 14-18, 2008.