Congenital heart disease is the most common birth defect in the world, affecting almost nine out of every 1,000 babies born. Michael Davis, Director of the Children's Heart Research and Outcomes Center (HeRO) under Georgia Tech and Emory University's Department of Biomedical Engineering, is dedicated to solving pediatric congenital heart defects using advanced technology, particularly stem cell research and 3D printing. The conditions that Davis and his lab deal with include hypoplastic left heart syndrome (HLHS) and left ventricular cardiomyopathy. Children’s Healthcare of Atlanta (CHOA) has been giving Davis and his team access to a large number of pediatric cardiac patients who are in need of new, experimental therapies.
“With pediatrics, clinicians are very open to collaborating and trying new procedures and therapies,” said Davis. “In the pediatric world, there are fewer options for these kids, and the parents and clinicians are hungry for new therapies to try.”
Davis’ research includes extensive work with stem cells. A few years ago, he noticed that during bypass surgery, small amounts of tissue were being removed to run the bypass tubing into the heart, and then discarded. Davis requested and was granted permission to use the tissue for stem cell research. He then began extracting and quantifying the stem cells, and discovered that young cells had more reparative qualities and released healing proteins when injected into damaged tissue.
Davis’ first clinical trial with the stem cells, the Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (ACT-HLHS) Trial, has been cleared by the FDA and will be taking place in the next few months. Clinicians will inject stem cells into the hearts of babies with congenital heart disease to improve the function of the heart.
“For a baby with HLHS, we are not going to re-grow the left ventricle, but rather try to strengthen and prevent deterioration of the existing right ventricle,” said Davis. “It sets the baby up for a successful repair surgery down the road.”
Davis observes the cells and gathers quantitative data on their behavior in his lab. He conducts his research on cord blood, bone marrow and cardiac stem cells. Along with Manu Platt, Diversity Director of STC on Emergent Behaviors of Integrated Cellular Systems (EBICS) at Georgia Tech, Davis has written a grant with the hope of combining all the cellular data from patients in three different clinical trials to create a large data repository of cell signals. Studying the signals, also known as protein secretions, can help Davis and Platt determine how effective certain cells are in treating diseases.
“These cells could be acting a number of ways, and we want to collect all the information we can, including their genome and what they release,” said Davis. “We essentially want to make equations to determine how cells will respond. We want to put the data together to create a treatment prediction.”
This information will allow the researchers to build a mathematical model that identifies the cell genome in order to predict what the cell will do in a clinical setting. They can then identify the best characteristics of these cells and determine which diseases they can target for repair.
“If we can study the cells and isolate their response, we will be able to provide personalized approaches to stem cell therapy '“ that's really what the field is currently lacking,” said Davis. “A patient could come in, and we could sequence their cells and know immediately what cells to inject for the best outcome. Different cells are going to have differing effects on each individual.”
Davis and his lab also use 3D printing to create valves, leaflets and patches. Biomedical engineering PhD candidate Aline Nachlas has discovered a material that will support the 3D printing of valve cells. The valves are made using skin cells from the patient, which minimizes the risk of organ rejection, and allows the organ to grow with the patient, meaning that a replacement will never be needed.
“We hope these cells will be able to print valves, or at least the leaflets that make up valves,” said Davis. “Currently, children are undergoing animal valve replacements, which are sometimes too big, and they don't grow with the child. This means more surgeries down the road to replace the valve, as well as high doses of immunosuppressants. We want to create a living valve that grows with the child.”
Davis’ lab is also working on a 3D printable patch that contains stem cells. The patch keeps all the stem cells in one place so that the cells can repair the surrounding tissue. The lab is looking to 3D print the patch scaffold with a decellularized pig material matrix.
“Very few people are trying to heal with 3D printed patches,” said Davis. “My lab is on the forefront of that research. We are trying to make a positive contribution in a sensible way.”
Davis hopes to focus more on 3D printing in the next five to 10 years so that he can advance regenerative therapies and bring them to as many pediatric patients as possible.
“My research may not always move at the speed I want, so I try to remember there is a bigger picture,” said Davis. “We are already helping many kids with CHD become healthier and stronger. But, I am always asking myself ‘what can we do better?'”
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