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Under the Microscope with Diego Correa, M.D., Ph.D.

Currently, people with type 1 diabetes who receive an islet transplant must take harsh anti-rejection drugs to prevent their immune system from destroying the new insulin-producing cells. But what if islets could be protected without these drugs within a site specifically designed to do just that? DRI scientists are now working to engineer BioHub platforms with safer and more targeted technologies that can help islets evade destruction by the immune system.

Among the methods being tested is the use of certain cells within the body that can provide a variety of therapeutic advantages to the islets and help them survive long term. One cell type in particular, mesenchymal stem cells (MSCs), have been investigated for years at the DRI due their powerful immunomodulatory properties among other benefits. One of the researchers at the forefront of this work is Dr. Diego Correa, assistant professor at the Diabetes Research Institute. An expert in mesenchymal stem cells, Dr. Correa has been working with MSCs for more than a decade to understand the way these cells behave in the body, how they function, and, in particular, how to utilize them in clinical applications for type 1 diabetes and regenerative medicine approaches.

In his lab, Dr. Correa and his team have been pursuing innovative approaches to co-transplant mesenchymal stem cells and islets, which have yielded some striking findings on how these cells block immune responses.

What is a mesenchymal stem cell?

Mesenchymal stem cells, or MSCs, are cells present in every tissue of our body, strategically located surrounding blood vessels. MSCs have been historically seen as progenitors (cells able to generate new tissues like bone, cartilage, muscle and fat), however, we have recently discovered that these cells can actually generate also key therapeutic effects after they recognize places of injury. These “medicinal” activities relate to the regulation of the immune system and, at the same time, the formation of new blood vessels and the prevention of scar formation, among other biological advantages. So in the end, these are essential cell types that we have in our bodies, naturally occurring, that we test for therapeutic purposes.

What benefits can MSCs bring to islet transplantation?

The DRI has spearheaded an innovative islet transplantation method with a resorbable scaffold in the omentum. We are advancing this strategy by engineering this biologic platform with MSCs as an important component. The premise is that after we transplant islets into a recipient, we need to induce immune tolerance so that the patient’s immune system does not react against these islets and destroy them. Base on the notion that MSCs have immunomodulatory effects (including local immunosuppression), we are trying to hijack those properties to help the transplanted islets evade the unwelcoming immune system of the recipient while improving their biological performance.

We now know that we have different subtypes of MSCs in our tissues and organs, independent of the source of the cells (e.g., bone marrow, fat tissue, etc.). In our lab, we are interested in identifying and characterizing those subtypes of MSCs based on distinct identities and functions. We documented a specific subpopulation of MSCs with intrinsic powerful activities in terms of modulating, or controlling, immune system responses. Additionally, those MSCs secrete various factors that induce the formation of new blood vessels, which are critical for carrying critical oxygen and nutrients to islets, assuring their survival and wellbeing. Consequently, by transplanting these MSCs together with islets, we are accomplishing two important goals at the same time: dampening the immune system attack on the islets and accelerating the rate of blood vessel formation that gives the islets an even better chance to survive.

What results have you seen by combining islets with MSCs?

Our strategy is to co-culture, or combine, the islets with the MSCs before transplantation. What we have seen so far in some of our analysis performed by various investigators at the DRI is that these two cell types, when they are co-cultured or put together in vitro [outside of the body] they actually coalesce and then function together. Some of these MSCs surround the islets, protecting them from an attack by the immune cells, while other MSCs enter inside the islet, stabilizing the blood vessels, which is one of the crucial steps for the durability and viability of the islets. What we want to do is to perfect the cell-based product before it’s transplanted into patients.

Why is the work underway with MSCs so exciting right now?

I have a very special passion for MSCs. It’s fascinating to work with them because I see how dynamic they are, how we can actually make them change the way they behave biologically in the petri dish and then in the body. There are other promising approaches being investigated by my team and other colleagues at the DRI using MSCs. Everything we’ve learned is so exciting and I think we are going after something extremely significant for the patients with type 1 diabetes. As I’ve stated before, stem cell-based therapy is no longer part of the medicine of the future, but certainly of the present.

(DRIFocus Spring 2018)

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