UNDER THE MICROSCOPE

Tracy Grikscheit, MD, discusses her groundbreaking clinical trial, how optimism drives her and why she was made for pediatric surgery.

In the operating room and clinic, Tracy Grikscheit, MD, treats children with disorders affecting the digestive tract. Sometimes, this means removing diseased or non-functioning sections of the intestines. If enough tissue is removed, children may require transplant surgeries or intravenous (IV) nutrition for the rest of their lives. As these treatments are incredibly challenging and have significant side effects, Dr. Grikscheit has developed a research program aimed at delivering better outcomes.

In her laboratory, she works in the realm of tissue engineering—the growth of new intestinal tissue to replace missing or diseased sections. Dr. Grikscheit’s preclinical studies have culminated in a method to grow induced pluripotent stem cells, or IPSCs, into fully functional tissue. Her already overlapping worlds of pediatric surgery and discovery science are about to converge even more as she edges toward a clinical trial.

Now in her 15th year at Children’s Hospital Los Angeles, Dr. Grikscheit talks about stem cell therapies, funding for research and why adding pictures to a wall means so much.

WHAT ARE YOUR ROLES AT CHILDREN’S HOSPITAL LOS ANGELES?

I came to CHLA right out of my fellowship, so I’ve been here 15 years. I recently became the Chief of the Division of Pediatric Surgery. Part of the time, I’m a surgeon taking care of children; part of the time, I’m leading my division. But I also run a research laboratory, working on stem cell therapies.

THAT’S A LOT OF ROLES. DOES IT FEEL LIKE A BALANCING ACT?

No, it’s all very synergistic. At the end of the day, everything I do is about optimism. I think most pediatric surgeons are optimists. It’s why we do what we do. We love seeing that we can fix a problem and then that baby thrives for the next 90 years. As a surgeon, when I see an unmet clinical need, I am very hopeful that, through science, I can make medicine better by finding a way to meet that need. And as a division chief, part of my job is to remove hurdles for those doing discovery or clinical work. It’s all about optimism, making things better.

WHAT LED YOU TO BECOME A PEDIATRIC SURGEON?

I always loved to do technical things with my hands, so in medical school I realized that surgery was a natural fit. Then when I rotated into pediatric surgery, the world just came together.

Pediatric surgery allows me to be the kind of doctor I want to be—I get to participate from the very beginning. I have great dialogues with the families, where we work together to decide how to proceed. I feel like I’m part of a team that is championing each child. And that’s how it should be.

DO YOU EVER GET THE CHANCE TO FOLLOW UP WITH YOUR FAMILIES DOWN THE ROAD?

Just today, actually. A dad brought in his little boy who I had treated a couple of years ago. If we didn’t intervene, his son would have died. Today he brought the child into the clinic just to show him to me, as if to say, you did this. And if I can do that 100 times, and have 100 wonderful kids running around who otherwise wouldn’t have been, then maybe I’ve earned my place in the world. We’re all here to do something positive, make a mark. [Dr. Grikscheit points to a wall, where there’s a corkboard covered with letters and pictures.] Here are some of my kids. These families are letting me know that they’re out there enjoying the world, and that’s really the whole reason we’re here.

SHIFTING TO YOUR RESEARCH, WHAT ARE YOUR GOALS? WHAT NEEDS ARE YOU TRYING TO MEET?

Sometimes children are born with disorders where a large section of the intestine simply doesn’t work. It could be that the tissue is diseased, or the digestive tract is missing the proper nervous system. Either way, we often have to remove sections of intestine.

If the condition is severe enough, the child will need an intestinal transplant or they’ll have to get IV nutrition. But transplants aren’t always successful, and IV nutrition keeps children alive but isn’t really a permanent solution. We need better options for these kids. And that’s where my lab work comes in.

HOW WILL RESEARCH PROVIDE BETTER OPTIONS?

If we could replace sections of tissue by helping the child regrow them, these kids could have a shot at eating normally and doing everything their peers are doing. Even though I run a discovery science lab, we will only pursue a research question if it’s going to directly lead to a future human therapy.

Discovery science for the sake of discovery is very important, and we depend on that foundation for our work. But we have a specific goal to get stem cell therapies out and available to children in need. And because we have been so focused, we are getting close to testing our stem cell therapy in a clinical trial.

HOW CLOSE ARE YOU TO GETTING STEM CELL THERAPIES INTO THE CLINIC?

We are currently working with the Food and Drug Administration (FDA) to initiate a clinical trial in the next year or two to help children with severe enteric neuropathy. These are children who are missing some or all of the nerve tissue controlling their digestive tract. It’s like having a roadway with no signs or traffic lights. The intestines are there, but there are no signals to get them to work.

In our experiments, we’ve been able to regrow the nerve cells and they’re fully functional. The goal is to rebuild the nervous system in the digestive tract without having to remove or replace the child’s intestines. After many, many years of experiments, we are ready to bring this therapy to our patients.

WHY STEM CELLS?

Stem cells are special because they are essentially waiting to be told what to do. With the right environment, they can become any kind of cell, and we’ve spent many years discovering the most effective ways to get them to grow into fully functional tissue.

WHAT ADVANTAGES WOULD YOUR STEM CELL THERAPY HAVE OVER CURRENT TREATMENTS?

Some babies with enteric neuropathy are so sick and they’re just too small to undergo a surgical procedure like a transplant, even if donor tissue is available. We don’t always know that a baby will be born with a poorly functioning digestive tract, so it would be a huge advantage to have a therapy ready immediately.

The stem cell therapy we are working on is essentially an “off-the-shelf ” treatment, meaning that once the clinical trials are complete and it is FDA-approved, it would be ready to go for any baby who needs it. And if we can help a child regrow the missing tissue themselves, we would eliminate issues like donor tissue availability and the risk of transplant rejection.

LAST YEAR, PROPOSITION 14 PASSED, GIVING $5.5 BILLION TO THE CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE (CIRM). HOW HAS FUNDING LIKE THIS IMPACTED YOUR WORK?

The people of California have driven my ability to make stem cell therapies for babies. CIRM funding isn’t just money. It’s a mindset that has really caused this area of research to bloom; it has helped to cultivate an entire field and a generation of scientists.

We’ve had many CIRM-funded students in our lab, and they have gone on to get advanced degrees and are working with stem cells. An entire network of people and field of research have arisen from the vision that the people of California had to make their state a leader in developing stem cell therapies to fill unmet clinical needs.

When the proposition passed, I had a video call with some other scientists who also championed the initiative. We all just looked at each other in awe and said, “Let’s do this. Let’s fix people.”

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