Advancing the Science

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January 28, 2020

A look into the RAD Labs: Vascular and interventional radiology translational research

By Advancing the Science contributor
Dr. Misra on left, explaining something to several members of his lab team, using white board and marker.
Sanjay Misra, M.D., says he finds mentoring young trainees and staff in his lab is both exciting and fulfilling.

By Maria Ly, undergraduate public affairs intern

Sanjay Misra, M.D., an interventional radiologist, in 2010 launched a lab focused on improving existing therapies and creating new treatments to help patients with renal disease.

Funded by grants from the National Institutes of Health, American Heart Association, and Mayo Clinic, the Vascular and Interventional Radiology Translational Research Lab has five postdoctoral researchers and a lab manager.

As one of just a few interventional radiologists with their own vascular biology lab in North America, Dr. Misra is excited and proudly uses his research to help patients.

"In my practice, my research is very relevant to the patient and improving therapeutic outcomes, so what we employ in our lab is a combination of animal models and biology to understand how to improve the procedures we are doing currently," Dr. Misra says.

An area of focus for Dr. Misra has been renal disease, where he has sought to understand why arteriovenous fistulas and grafts, used for providing patients with vascular access for hemodialysis, develop stenosis and fail.

About 700,000 patients in the United States have end-stage renal disease and the majority of them require hemodialysis for the purification of their blood. A well-functioning hemodialysis arteriovenous fistula is the preferred vascular access.  Currently, the average patency of these arteriovenous fistulas is 60 percent in one year. In order to maintain patency, angioplasty is the preferred endovascular technique and its patency at one year is only 50 to 70 percent. There are no effective therapies to prevent blockages from occurring in arteriovenous fistulas.

purple-stained cells on screen of electronic microscope, gloved researcher holding clear container with purplish liquid in place on microscope tray
Fat-derived mesenchymal stem cells

Dr. Misra initially researched the failure of surgical fistula placement, which led to an investigation into why angioplasty does not work well when treating fistula failures.

Dr. Misra and his colleagues created animal models to understand the biology of arteriovenous fistula failures. They combined this with cell culture experiments, and his team learned that this set of "biological tools" could be used in other areas — such as with kidney injury caused by the use of iodinated contrast administration into the blood vessel and understanding why vascular malformations form.

Since the start of the lab, Dr. Misra and his colleagues have been conducting studies to create therapies to improve the outcomes of current procedures.

"There are several things I consider when thinking about this problem. One, I try to look at, how can we design a therapy that interventional radiologists, surgeons, cardiologists, and other proceduralists would want to use every day?" Dr. Misra says. "Number two, can we design a therapy that can improve our procedural outcomes beyond what we’re getting today? And number three, can we design something that will work in the next five years that we can test in humans in a phase 1 clinical trial?"

Through their stem cell research, Dr. Misra and his colleagues began a first-of-its-kind phase 1 human clinical trial with about two dozen patients to test whether a patient’s own stem cells isolated from fat can prevent venous stenosis formation. Dr. Misra calls this one of his proudest achievements.

"We’re going to start using stem cells with angioplasty — that’s our next goal," Dr. Misra says.

Along with improving procedural outcomes, Dr. Misra and his colleagues are in the process of exploring and improving drug therapies.

In the lab, Dr. Misra and his colleagues discovered an orphan drug, calcitriol tagged to nanoparticles composed of bio-absorbable poly lactic-co-glycolic acid (PLGA) that inhibits stenosis formation in dialysis arteriovenous fistulas. The drug is part of a National Institutes of Health grant and was recently issued a method patent. This was the lab’s second patent.

Another therapy in development is an orphan drug that prevents kidney injury in animal models if given before iodinated contrast administration.

"Science is a team sport. I think being at a place like Mayo allows you to tap into other parts of the team."

Sanjay Misra, M.D.

Aside from renal disease, the lab also studies a rare condition where malformations, called hereditary hemorrhagic telangiectasia, form in patients. In patients with this condition, pulmonary artery to vein malformations occur which can lead to hypoxia, stroke, heart failure and other problems. These are treated with embolization, in which platinum coils are deposited to stop the malformation from growing or rupturing. Dr. Misra and his colleagues aim to understand the biology of malformations associated with hereditary hemorrhagic telangiectasia to improve embolization treatment outcomes using adjunctive drug therapies. About 20 percent of these patients require multiple procedures to close the malformations.

"That’s sort of what’s different from my lab compared to an imaging lab — we try to understand why our current interventions and procedures do not work well and try to improve these therapies by combining with drugs, cells, or other biologics in a way that we can help our patients in a short period of time," Dr. Misra says.

The lab also allows Dr. Misra opportunities to mentor young staff, some of whom have gone on to receive grants of their own and become assistant or associate professors.

"Mentoring young trainees and staff is very exciting and fulfilling at the same time," he says. "Helping them succeed is important in helping develop the next generation of biomedical workforce so that we can improve our knowledge and understanding of human disease."

The work of the Vascular and Interventional Radiology Translational Research Lab is made possible because of grant funding and supporters outside of the lab, Dr. Misra says.

"Science is a team sport. I think being at a place like Mayo allows you to tap into other parts of the team," he adds. "We work in a very team-oriented way. We work with surgeons, kidney doctors, basic scientists, drug delivery people, also people not at Mayo. I think you need to have a really broad perspective when you’re thinking about this.

"Our common goal is to help patients."

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Tags: biomedical research, clinical trials, dialysis, kidney disease, medical innovation, nanomedicine, News, orphan drug, radiology, research, research education, Sanjay Misra, stem cells, team science

An enlightening post, thank you.
I believe a nephrology colleague at Mayo is running a trial of Adipose derived Mesenchymal cells to halt progression of chronic kidney disease.

Mohamed Salah Noshi MD,FACP.

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