Jeff Bulte on tracking cells through their journey through the body:
As a cell imaging specialist, what do you do?
BULTE: The goal of my group is to develop tools and techniques for tracking cells to eventually help physicians do clinical studies. We are really cell engineers that manipulate cells by putting contrast agents, labels and genes in them and by doing so develop tools that the treating physician can use to see cells non-invasively without the need for multiple biopsies.
Have any of your tools made it to the clinic?
BULTE: Yes, we have been tracking cells that are used in cancer vaccines. Currently, we irradiate tumor cells, so they cannot divide anymore, and we label these tumor cells with magnetic particles that appear black on MRI scans. Then, we inject the cells in the skin so the patient can develop an immune response. The immune cells in the body eat up these particles together with the cancer cells, so when they travel in the body, we can see the particles with an MR scanner. As of today, there have been at least 5 clinical studies using the method (that I originally developed at the NIH) to evaluate cell therapy in various diseases ranging from from melanoma to traumatic brain injury, diabetes, and multiple sclerosis.
What else is in the works?
BULTE: We also label pancreatic islet cells that make insulin to restore blood glucose levels as a potential therapy for treating diabetes. These techniques are still being developed in animals. Currently the problem with transplanting cells in patients is the body’s immune response that attacks and kills the injected cells. Doctors need to give immunosuppressive drugs to these patients and somehow coincidently these drugs are very toxic to the transplanted cells.
We are now encapsulating the islet cells in special spheres that are made out of seaweed, like a kind of a hydrogel, which protects them from the immune system. Then we label the capsules with contrast agents like gadolinium, gold or magnetic nanoparticles. We can see by X-ray, ultrasound, and MRI if the cells are injected correctly and if they are surviving the implantation process.
Can this technique be used for other therapies?
BULTE: Eventually I think these techniques will be important in any form of cell therapy that is done in patients. Sometimes a very precise injection is required in the spinal cord, the brain or the lymph node. Some physicians are just poking around with their needle and they don’t know if the cells reach their targeted therapy site. But, if you use real-time MRI guided injections, you can precisely see the needle and also see the injected cells. So, if the cells don’t get to the right place, the doctor can see that and they can give the patient another injection to correct the situation.
Do cells have to be labeled with metal to be detected by MRI?
BULTE: Not always, and we are actually working on developing the “holy grail” of labels--an MRI reporter gene. This technique uses proteins and doesn’t use any metal. This new MRI technique called CEST imaging (for Chemical Exchange Saturation Transfer) detects special chemical groups on amino acids and peptides. We are combining different types of these proteins in different cells, and we are even trying to develop multicolor MRI.
--Interviewed by Vanessa McMains
Jeff Bulte on labeling and tracking stem cells used for therapy: