Worlds First Stem Cell Trial for CF Under Way at UH Rainbow

Study is first step toward goal of developing therapy to quell CF’s lung inflammation

UH Innovations in Pediatrics – Winter 2018

James Chmiel, MD

Could human adult mesenchymal stem cells (hMSCs) hold the key to reduced inflammation and infection among patients with cystic fibrosis (CF)? A first-in-the-world clinical trial at UH Rainbow Babies & Children's Hospital is aiming to find out.

“When these stem cells are infused, they go to sites of infection and inflammation,” says pediatric pulmonologist James Chmiel, MD, Director, Cystic Fibrosis Therapeutics Development Center, UH Rainbow Babies & Children’s Hospital and Professor of Pediatrics, Case Western Reserve University School of Medicine and principal investigator of the trial and Director of the Cystic Fibrosis Therapeutics Development Center at UH Rainbow. “Essentially, the cells monitor what’s going on in the environment and respond to it in an attempt to bring the abnormal environment back into equilibrium. In this case, these stem cells secrete a natural defensive molecule against bacteria and also secrete anti-inflammatory molecules. In CF, the inflammatory response is really out of proportion to the burden of infection, which damages the lung.”

Study volunteers in the CF stem cell trial at UH Rainbow are all 18 years and older. They receive an infusion of allogeneic human mesenchymal stem cells (hMSC) – adult stem cells collected from the bone marrow of healthy and rigorously scrutinized volunteers. Study volunteers are then monitored for 24 hours in the hospital and at study visits one week, two weeks, four weeks, three months, six months, and twelve months after the infusion, where Dr. Chmiel and his colleagues perform a physical exam and review patient diaries, interval history, pulmonary exacerbations, spirometry, and safety laboratory results. The researchers are also collecting blood and sputum samples from study participants to test for inflammatory biomarkers.

The goal of the prospective, dose-escalation, open-label study is to determine whether hMSC infusions are safe and well tolerated and to establish the maximum tolerated dose.

So far, Dr. Chmiel says, the results are encouraging.

“We’ve gotten through the first dosing group and we’ve started to enroll the second dosing group,” he says. “This is an open-label study, so everyone is receiving stem cells. So far, the stem cells appear safe and well tolerated. That’s really all we know at this point because it’s so early on. We won’t know until the study is over what impact they’ll have against infection and inflammation. But ultimately, we’re going to learn a lot of things from this study that can be used in future stem cell clinical trials.”

Dr. Chmiel credits the collaboration between physicians and basic scientists within the Divisions of Pediatric Pulmonology,

Hematology/Oncology, and the National Center of Regenerative Medicine at Case Western Reserve University with bringing this clinical trial to fruition. The National Center for Regenerative Medicine is a consortium supported by University Hospitals, Cleveland Clinic and Case Western Reserve University.

“We have nine PhD scientists whose primary appointments are in pediatric pulmonology; they are employed by Case Western Reserve University School of Medicine but also have appointments within our division,” he says. “Through collaboration with our PhD and MD scientists – especially Tracey Bonfield, PhD, in our division and Hillard Lazarus, MD, professor emeritus of hematology/oncology, and Arnold Caplan, PhD, in biology, and in conjunction with the National Center for Regenerative Medicine, we have the very first stem cell study in CF.”

The CF stem cell trial at UH Rainbow is funded by the Cystic Fibrosis Foundation. It is part of an extensive pediatric pulmonology research portfolio that includes eight active studies in asthma, 29 active studies in CF, one active study in pulmonary hypertension and two active studies in primary ciliary dyskinesia.

“We’re fortunate because our patients can benefit from the legacy of research here at UH Rainbow Babies and Children’s Hospital,” Dr. Chmiel says. “When you have an active research program, it’s exciting for us as investigators to be on the cutting edge. But really what it does is to allow us to offer opportunities for our patients to avail themselves of these new therapies before they’re commercially available.”

For more information on the CF stem cell trial at UH Rainbow, please email Peds.Innovations@UHhospitals.org.