Children's Heart Research Lab
The University of Maryland Children’s Heart Program laboratory focuses on the application of stem cell-based therapies in children with congenital heart disease.
Researchers are studying how stem cells can improve the heart function and how stem cells can be used in tissue-engineering cardiovascular structures for children. Results from the lab were the first to report the characterization of resident cardiac stem cells in children with congenital heart disease. Now, research is focused on determining the mechanism of how the pediatric-derived cardiac stem cells can regenerate the heart.
Contributions to Science
Characterization of resident cardiac stem cells
The University of Maryland Children’s Heart Program’s researchers are interested in studying the biology of resident cardiac stem cells in children. The lab’s findings first described the presence of cardiac stem cells in the myocardium of congenital heart disease patients and showed that, when isolated and expanded, these injected cells can regenerate. Studies on cardiosphere-derived cells (CDCs) focus on:
- Their allogeneic properties
- How their chronological and physiological age affect their functional activity, influencing their regenerative abilities in direct relation to paracrine factor secretion
- Why neonatal CDCs secrete more VEGF-A and Angiotensin II, making n-CDCs more regenerative than adult CDCs
- Why CDCs from failing heart have stronger regenerative abilities than normal heart muscle tissue
In particular, we are studying novel cellular pathways present in their secretome and micro-RNAs present in their exosomes.
Application of stem cells in pediatric heart failure
The ultimate goal for studying the biology of resident cardiac stem cells and mesenchymal stem cells is to apply this cell-based therapy to congenital heart disease patients who suffer from heart failure.
The Children’s Heart Program recently obtained two INDs from the FDA to use c-kit+ cardiac stem cells and mesenchymal stem cells in Hypoplastic Left Heart Syndrome patients. These HLHS patients do well initially with surgery but then develop right heart failure.
The study will use cardiac stem cells or mesenchymal stem cells as an adjunct to the standard surgical therapy, anticipating regeneration or a boost in function of the right ventricle. This will be one of the first stem cell trials in congenital heart disease patients in the country.
Tissue-engineering pulmonary valves with biodegradable scaffolds
The Children’s Heart Program’s lab focuses on tissue-engineering pulmonary valves using biodegradable polymers and developmental pathways for congenital heart disease patients. The lab was the first to create a pulmonary valve on a biodegradable polymer by using an in vitro pulse duplicator system to provide a biomimetic environment during tissue formation to yield more mature implantable heart valves derived from autologous tissue. These autologous tissue-engineered valves functioned up to five months and resembled normal heart valves in microstructure, mechanical properties and extracellular matrix formation.
To better manufacture a pulmonary valve, researchers:
- Studied how native valves are formed during development.
- Demonstrated that aortic valve endothelial cells undergo transforming growth factor-beta-mediated and non-transforming growth factor-beta-mediated transdifferentiation in vitro.
- Demonstrated the importance of NFATc1 in causing VEGF proliferation of pulmonary valve endothelial cells.
Stem Cells Application for Tissue Engineering
The Children’s Heart Program lab’s researchers have an interest in using stem cells in creating tissue-engineered cardiovascular structures for congenital heart disease patients.
Research demonstrated that endothelial progenitor cells can function similarly to arterial endothelial cells and therefore confer long-term patency of our vascular grafts.
Another focus is creating pulmonary valves that grow with congenital heart disease patients. The creation of biodegradable scaffolding seeded with mesenchymal stem cells was initially successful.
Recently, our research demonstrated for the first time the feasibility to generate a patient-specific valve on a decellularized pulmonary valve scaffold using induced pluripotent stem cells.