Q&A With Arun Sharma, PhD: The Heart Modeler

Cancer treatments save lives. They also might cause heart damage in the process.

Cedars-Sinai research scientist Arun Sharma, PhD, wants to be able to predict when this might happen. As the head of a new laboratory in the Cedars-Sinai Board of Governors Regenerative Medicine Institute, the Department of Biomedical Sciences, and the Smidt Heart Institute, Sharma is creating models of the human heart by using stem cells derived from blood. The goal is to better personalize cancer treatments. The Cedars-Sinai Newsroom recently sat down with Sharma to learn more about his leading-edge science. 

Newsroom: How are you modeling cardiovascular disease in your lab?
Sharma: We use induced pluripotent stem cells—blood cells that have been reprogrammed—and turn them into beating human heart cells. This is exciting technology because for the first time, we can mass produce person-specific human heart cells by the billions. It’s a process performed in vitro, which just means growing cells in a petri dish. And we’re hoping to use these cells to predict what's going to happen to a real patient in a clinic. Eventually, we’ll be able to predict if a person might experience heart damage after cancer therapy. We will take a small blood sample from a patient, just a little more than a drop of blood. We will then make their induced pluripotent stem cells, turn them into heart cells in a dish, and then treat those heart cells with chemotherapy drugs to see a potential response.

We are currently working on a project focused on doxorubicin, a breast cancer drug well known to cause heart damage. We are investigating a potentially safer version of this drug.

Newsroom: How exactly do you create heart cells?
Sharma: Stem cells are cells in the body that can turn into other cells. Stem cells of the blood, for example, can turn into all the other cell types found in the blood, like the platelets, the white blood cells, and red blood cells. We start from a small sample of an individual's blood. From that sample, we extract the white blood cells, and then we subject the cells to four different factors, which allows them to turn into stem cells. That takes about one month. From the stem cells, we create beating human heart cells using another cocktail of factors that have been developed over the last 10 years or so. That process takes a couple of weeks.

After about a month and a half, we can go from a small sample of a person’s blood to creating that person's own beating heart cells outside of their body. It sounds like science fiction, but we can actually do this.

Newsroom: What discoveries has your lab made so far?
Sharma: This wasn't the initial focus of our work, but during this pandemic, we wanted to see if the virus that causes COVID-19 directly infects the cells of the heart. We used our stem cell-derived heart cells and collaborated with biologists at UCLA to infect these heart cells with the coronavirus. We were able to find that, indeed, the cells of the human heart can be directly infected by the coronavirus in certain circumstances, typically in cases of severe disease. This has been confirmed by clinical case reports. In a follow-up study, we've been able to identify new antiviral compounds that may alleviate or reduce some of the impact of the virus on the heart.

But the main focus of my work is looking at the effects of cancer treatment on the heart. I've also been able to make a model that has the blood vessel cells of the heart and the heart muscle cells, all in one 5 centimeter-by-2 centimeter chip. It's a new-and-improved way to study heart disease outside of the body.

Newsroom: Why did you decide to focus your research on heart disease caused by cancer treatments?
Sharma: For one, cancer and heart disease are two of the leading causes of mortality and morbidity in the world. And, two, as new, leading-edge cancer treatments emerge, a major concern is the potential for unintentional damage to the heart. This concern is the foundation for the emerging medical field of “cardio-oncology.” There is a need to be able to predict who might develop heart damage caused by cancer treatment in a safe "pre-clinical" environment using these heart cells in a dish. 

Newsroom: You’ve also sent stem cells into space. Why?
Sharma: This is somewhat unrelated to our cancer work, but we want to figure out what happens to the body in space to help astronauts stay healthy. But, also, a lot of what happens in space mimics the phenomenon of aging: Your bones degrade, your muscles degrade, the size and structure of your heart changes. Thus, one application of our work is to study aging in an accelerated fashion in space by using stem cells.

Newsroom: What can people do now to protect their hearts?
Sharma: There are some amazing technologies and clinical applications being implemented here at Cedars-Sinai. But I still think the best thing is to take care of our hearts every day by eating right and exercising.  

Read more on the Cedars-Sinai Blog: The Untapped Potential of Stem Cells