In a first-in-children randomized clinical study, medical researchers at the College of Maryland School of Medicine (UM SOM) as well as the Interdisciplinary Stem Cell Institute (ISCI) at the University associated with Miami Miller School of Medicine have begun assessment to see whether adult stem cells derived from bone marrow benefit children with the congenital heart defect hypoplastic still left heart syndrome (HLHS).

O SOM surgeons are injecting the cells into the babies’ minds during open-heart operations at the University of Maryland Clinic. ISCI is supplying the stem cells for the techniques.

Even with extensive surgical treatments, HLHS babies can still do not have optimal outcomes. The researchers hope the cells increases the babies’ chances of survival as HLHS limits the particular heart’s ability to pump blood from the heart to the entire body.

“The premise of this clinical trial would be to boost or regenerate the right ventricle, the only ventricle during these babies, to make it pump as strongly as a normal remaining ventricle, ” says lead researcher Sunjay Kaushal, MARYLAND, PhD, associate professor of surgery, University of Baltimore School of Medicine and director, pediatric cardiac surgical procedure, University of Maryland Medical Center. “We are hoping this particular therapy will be a game-changer for these patients. ”

Kaushal says the first two patients, who were both four-months-old when the stem cells were injected, are doing well right after their surgery.

Mesenchymal Stem Cellular material

This is the first HLHS research in the usa to use stem cells known as allogeneic mesenchymal stem cellular material (MSC). Allogeneic cells can be used in other human beings without generating an immune response, which could cause the body to deny the cells. Additionally , these cells are a type of adult come cell (found in both children and adults), unspecialized tissue that can develop into tissue- or organ-specific cells. MSCs could be harvested in advance, expanded in culture, and stored to be used later.

The allogeneic nature of the MSCs makes it possible for stem cells from one bone marrow donor to give all the stem cells for this study. Researchers elsewhere take a different approach to strengthen the HLHS heart, with autologous cells, stem cells taken from the HLHS patient’s personal umbilical cord, for use in that specific patient.

In adult patients, MSCs in the heart have been proven to reduce scar tissue, reduce inflammation, cause new small ships to grow, and stimulate the heart to regenerate itself, leading to heart muscle cells and cardiac stem cells to develop.

“We’ve had incredible results in using mesenchymal stem cells to regenerate damaged heart muscle in grown-ups, ” says Joshua M. Hare, MD, ISCI founding director and sponsor of the study. “This is the very first time these types of cells are being used in infants, so this is very thrilling. ”

The Interdisciplinary Stem Cell Company has grown from a local research center to a national cellular manufacturing facility. ISCI provides cells for the Cardiovascular Cell Treatment Research Network, has been named a Production Assistance intended for Cellular Therapies Center by the National Heart, Lung plus Blood Institute, and has been conducting research in come cell use for cardiovascular repair since 2008.

Study Details

HLHS is one of the most challenging and complex congenital heart illnesses to treat. The Centers for Disease Control and Avoidance (CDC) estimates that about 960 babies in the United States are usually born each year with HLHS. For unknown reasons, the particular heart’s main pumping chamber, the left ventricle, will not develop completely during a critical growth period just prior to delivery. The right ventricle normally pumps blood to the lungs with low pressure to be oxygenated, while the left ventricle forces blood at high pressure through the aorta to the entire body. Within children with HLHS, the right heart assumes the extra workload, temporarily supporting the circulation to both the lungs plus body. That stress can cause the right heart to fall short and the baby to die.

Current HLHS treatment options are either a heart transplant or a series of 3 open-heart reconstructive surgical procedures to connect the left and right sides from the heart. However , even with a transplant or the reconstructive medical series, children with HLHS have an average five-year success of only 50-60 percent.

In this Stage 1 safety and efficacy study, allogeneic MSCs are usually injected into the heart muscle during the second of the 3 reconstructive surgeries, typically performed at approximately four a few months of age.

A total of 30 patients along with HLHS will be enrolled in the study. Fifteen patients will obtain six-to-eight stem cell injections each, based on the size from the heart, while 15 control patients will not receive the cellular material. This is an open-label trial, in which researchers and participant family members will know whether or not the cells are administered.

Basic Science

Kaushal laid the particular groundwork for this trial eight years ago as he began discovering the possibilities of stem cells to strengthen children’s minds. Kaushal says he and his team developed many versions trying to understand how these cells work in the laboratory just before moving to a clinical application. “There’s a lot of basic technology behind what we’re doing. I want to make sure that what we go after is rigorous in the laboratory, to make sure that we’re providing the very best therapy for these little kids. ”

Various researchers at the School of Medicine’s University of Baltimore Center for Stem Cell Biology & Regenerative Medication have added their expertise to the effort, collaborating along with Dr . Kaushal to understand and develop stem cell treatment for children with heart failure.

“Dr. Kaushal and colleagues have discovered that the failing neonatal coronary heart is actually a rich source of cardiac stem cells, but the current stem cells in the hearts of these babies are not adequate to overcome HLHS, ” says Curt I. Civin, MD, professor of pediatrics and physiology, director from the Center for Stem Cell Biology & Regenerative Medication, and Associate Dean for Research at the University associated with Maryland School of Medicine. “We are close to knowing one mechanism underlying this insufficiency. This line of studies a key part of our quest to use stem cells an automobile accident, cure and prevent severe diseases in children and adults. ”

In previously published research, Kaushal demonstrated that will mesenchymal stem cells can restore function in a pre-clinical model replicating many of the features of HLHS. The stem cellular material remodeled the heart muscle (myocardium) similar to normal myocardium. Come cells in the heart may also secrete growth factors favorable to forming heart muscle and keeping the muscles from dying. “These key findings suggested these cellular material would work for HLHS patients, ” says Kaushal.

While stem cells have been used to regenerate grownup hearts, Kaushal says improvements have been marginal. His study suggests results may be better in pediatric hearts: “The heart is able to remodel better in a younger patient compared to an older patient, because the body is still growing, good things are getting on, and things are not deteriorating. ”

Civin, a pediatric oncologist, says his very first individual as a pediatric intern-in-training years ago was an infant with HLHS. “I’ve seen how devastating HLHS can be for children and their families. I’m thrilled with the launch of this first-in-children stem cell therapeutic trial, and look forward to the affected person outcomes. ”

The Department of Surgical procedure at the University of Maryland School of Medicine provides funding for the clinical costs associated with this trial. “Dr. Kaushal’s research will give families with a devastating diagnosis hope for a much better outcome for their child, ” says Stephen T. Bartlett, MD, the Peter Angelos Distinguished Professor; Chair from the Department of Surgery at the University of Maryland College of Medicine; and Surgeon-in-Chief and Executive Vice Chief executive of the University of Maryland Medical System. “The Section of Surgery’s funding of this project demonstrates the essential need and the promise this research holds for an extremely at-risk population who only have a 50/50 shot in survival with current treatment protocols. ”

“This novel therapeutic approach exemplifies how our teachers are unrelenting in their search for new ways to improve the wellness of some of our tiniest and most vulnerable patients, inch says E. Albert Reece, MD, PhD, MBA, vice president for medical affairs, University of Maryland; the particular John Z. and Akiko K. Bowers Distinguished Teacher; and dean, University of Maryland School of Medication. ” This stem cell therapy may provide a brand new treatment option not just for patients with HLHS, also for patients with other congenital heart problems. ”