Under the Microscope with Norma S. Kenyon, PH.D.
At the DRI, we’re working to discover a biological cure for type 1 diabetes. To accomplish this, we are pursuing approaches to eliminate autoimmunity and permanently restore the natural ability to sense blood sugar and release the precise amount of insulin to maintain normal glucose levels.
We have already shown that replacing the lost insulin-producing islet cells can give patients back the ability to naturally produce insulin. While we are extremely encouraged by this progress, we’re continuing to overcome the remaining challenges.
Among these is the need to limit the inflammation that occurs after transplantation. When you get a splinter in your finger, the skin around it usually turns red and becomes inflammed. That’s our immune system at work trying to protect us from germs that could harm our bodies. The response – the inflammation – also happens when insulin-producing cells (or other tissues) are transplanted into a patient. The problem is that inflammation can adversely affect the survival and function of the islet cells. So, scientists here at the Diabetes Research Institute are trying to find ways to reduce or prevent this inflammatory response.
The DRI’s Dr. Norma Sue Kenyon, Martin Kleiman professor of surgery, microbiology and immunology, and biomedical engineering at the University of Miami, is leading the effort to reduce inflammation. One promising area of focus is on Mesenchymal Stem Cells (MSCs) – which Dr. Kenyon and her team discovered have a beneficial effect on transplanted islets. MSCs are found naturally in our body’s own bone marrow and have the unique ability to not only reduce inflammation, but repair damaged tissue and stimulate the growth of blood vessels. They may also play a role in the survival and function of insulin-producing cells. For all these reasons, it is believed MSCs can enhance the use of cell-based therapies for the treatment of diabetes.
How did you first discover Mesenchymal Stem Cells (MSCs) had potential as a therapy for the treatment of diabetes?
Many years ago, we conducted a study to see if donor bone marrow cells (DBMC) could be used to help diabetes patients better tolerate transplanted insulin-producing cells. At the time, little was known about MSCs and the primary goal of that study was to determine if MSCs, given intravenously with the bone marrow cells, could enhance bone marrow engraftment. Because they were believed to have anti-inflammatory properties, we also decided to co-transplant MSCs with islets to see if they could prevent the inflammatory response associated with transplantation of islets into the liver. We discovered that the MSCs did have a positive impact on islet function.
In that pre-clinical study, recipients that received MSC/islet co-transplants had more than double the levels of c-peptide production compared to those that received islets alone, indicating increased insulin production and better functioning islets.
Since that initial discovery, how has your study of MSCs evolved?
Follow-up pre-clinical studies continue to confirm our initial findings. It’s just astonishing to me how, with a small amount of islets, we’re able to reduce dependence on insulin. The results are encouraging and that work continues. At the same time, we’re collaborating with the DRI Tissue Engineering Team to incorporate MSCs into engineered structures designed to house and protect insulin-producing cells.
What are the next steps?
We are learning more about how MSCs work by tracking their movement. Thanks to funding from our Diabetes Research Institute Foundation, we’ve been able to collect preliminary information on how to track these cells using magnetic “markers.” Having an understanding of where cells go and what they do is key to conducting safe and effective clinical trials.
What other challenges remain as you explore the potential of MSCs as an effective therapy for diabetes?
We know that not all MSCs are created equal. You can look at the surface of the cell and say it has the right shape and appearance under the microscope, but that doesn’t mean it’s manufacturing all those wonderful molecules that are anti-inflammatory. So, if you just take a population of cells and start transplanting them, you’re going to get a mixed bag of results. One of our next goals is to characterize MSC cells – to clearly identify which ones make the necessary molecules and, as a result, determine which MSCs are optimal for use in clinical trials.
What is your ultimate hope for the use of MSCs to cure those now living with diabetes?
These naturally-occuring cells have the potential to benefit diabetes patients in many ways. First, if MSCs can reduce or prevent the inflammation that occurs after transplantation, we can enhance the long-term viability of the islet cells needed to restore natural insulin production. Secondly, when more cells survive, fewer will be needed for transplant – perhaps as few as one third the islets we use now – which is critical because one of our other great challenges is that donor tissue is in short supply. And finally, there’s also evidence that MSCs can reverse rejection, which means we may be able to use them to lower the amount of immunosuppression (anti-rejection drugs) that islet transplant patients must now take long term.
(DRIFocus Spring 2010)