Live Cell Biobank for Individualized IBD Therapies

Live Cell Bank Could Pinpoint Individualized IBD Therapies

Date: 31 Aug 2021

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Researchers at Weill Cornell Medicine in New York City believe their leading-edge repository of tissue samples can generate more answers for clinicians who treat children with inflammatory bowel disease. In place of snap-frozen samples, Weill Cornell’s IBD biobank uses cryopreservation to keep cell samples alive and study them over the long term.

The team at Weill Cornell actually prefers to call their biobank a Live Cell Bank to distinguish it from other biobanks that don’t work with live cells, said Robbyn Sockolow, MD, the chief of the Division of Pediatric Gastroenterology and Nutrition. “The science behind what we do is really phenomenal. We have a true partnership with basic scientists,” she said.

Established in 2015, the biobank now contains samples from over 2,000 patients, nearly 700 of them pediatric. Around 150 are returning donors, giving the team at Weill Cornell the ability to conduct longitudinal studies.

The team collects a range of samples from donors during the colonoscopy, including peripheral blood and cryopreserved peripheral blood mononuclear cells, immune cells from the lamina propria for functional studies, and biopsy tissues from the intestinal epithelium for transcriptome and proteomic analyses. Stool samples also are collected for viral, fungal and bacterial microbiome analysis.

We can create a fairly comprehensive picture using all these platforms,” David Artis, PhD, the director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell, said. “On a number of levels, we’re getting a better understanding of the heterogeneity of the disease.

Until recently, gastroenterologists have had limited ability to profile IBD. Fresh samples had to be tested immediately, which prevented extensive profiling or more complicated study designs. Snap freezing preserved but also killed samples. The ability to preserve live cells means researchers have more time to study the nuances of an individual’s disease. There are three recognized types of pediatric IBD, but Dr. Artis said he expects that number to grow, thanks to research using the biobank.

Tissue Cell

“The way this is being done at Weill really affords the ability to have patients’ samples studied in a very detailed way,” Scott Snapper, MD, PhD, the chief of gastroenterology, hepatology and nutrition at Boston Children’s Hospital, said. The team can essentially grow “mini guts” in a dish based on a single patient, he said, and learn the specific underpinnings of their disease.

More than just understanding IBD, the biobank is a “resource that would allow us to do preliminary translational research with patient samples,” Dr. Artis said. That includes testing different treatments on a patient’s samples to identify the most effective treatment for their individual disease.

“For IBD patients, it’s currently unclear what medicine to give what patient at what time,” Dr. Snapper, who is not directly involved in the project, said. Finding the right treatment for a given IBD patient is trial and error. It’s a physician’s best guess based on available trends and data. But Weill Cornell’s biobank could allow them to ascertain whether a patient has certain molecular signatures.

In Search of: Personalized IBD Therapies

Researchers have already identified a few predictive genetic markers for certain IBD therapies. For instance, a 2017 study in Nature Medicine reported that oncostatin M predicted failure of anti–tumor necrosis factor agents. Another study in Gastroenterology found that in patients who didn’t respond to anti-TNF agents, higher baseline serum concentrations of interleukin-22 were associated with a greater likelihood of response to MEDI2070. But these markers have never been studied as a part of treatment choice, Dr. Snapper said. The hope, however, is that Weill Cornell will soon be able to tell—based on a patient’s extensive profile of genetic markers, microorganisms, RNAs, proteins and metabolites—which treatment fits best.

Getting the treatment right for patients early on could make all the difference in their long-term health, Dr. Sockolow said. The correct treatment in the first few months of symptoms can quell the inflammation and prevent damage, essentially restoring the patient’s health back to their pre-IBD state, she said. But if early treatments aren’t successful, fibroblasts can form and lead to more lasting damage.

The same kind of translational research also may aid the investigation of nutritional interventions in IBD. “We would love for diet to participate way more in IBD treatment, but we are still in the infancy” stage, Dr. Sockolow said. She said parents would leap at the opportunity to employ nonpharmacologic interventions. But because of heterogeneity of the disease and the challenge of human nutritional studies, making broad nutritional recommendations is difficult.

But certain strategies could be very effective on an individual basis. Dr. Artis is particularly interested in looking at different fiber types and contents. High-fiber diets have worked wonders in mouse models, he said, but such diets are controversial because many recommendations for IBD call for patients to avoid fiber. It’s likely that it comes down to the specific fiber type, because “some can activate the immune system and some can switch the immune system off,” he said. That’s something they could eventually examine on a patient-by-patient basis.

Right now, the gastroenterologists and researchers at Weill Cornell are collecting samples and analyzing them extensively. There’s enormous potential for research and clinical practice, Dr. Snapper said, but “until you—in a prospective way—test your hypothesis, until you actually do the study, you don’t know.” Still, he expressed confidence in the team carrying the project forward: “They have a star-studded group of investigators and clinicians. There are maybe a half a dozen groups around the world that can do that sort of thing, and they’re one of them.”

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