Researchers at the Ted Rogers Centre for Heart Research have developed an innovative approach to better understanding the complex signaling mechanisms underlying heart failure. A recent publication in the Proceedings of the National Academy of Sciences (PNAS) offers...
By Agnes Soos
When we think about repairing or replacing damaged heart tissue, the patient group that most often comes to mind are adults. Yet there is another group for whom engineered heart tissue can have life-saving outcomes: infants with congenital heart defects.
One in 3,600 children is born with Tetralogy of Fallot (ToF) – a congenital heart defect targeted in many ways by the Ted Rogers Centre. ToF is marked by abnormalities in the development and organization of the heart’s various structures. Pulmonary valve hypoplasia – where the valve is absent or incompletely formed – is characteristic among these young patients. Unfortunately, traditional methods of repair invariably yield sub-optimal function and often lead to ventricular dilation, arrhythmia, and risk of sudden cardiac death at adolescence.
Shouka Parvin-Nejad is a University of Toronto PhD student working in the Centre’s Translational Biology and Engineering Program. Co-supervised by Ted Rogers Centre Scientific Lead Craig Simmons and Dr. Christopher Caldarone (SickKids), she is aiming to develop a tissue-engineered heart valve for these pediatric patients.
Tissue needs to grow as the children grow
Such engineered valves are dependent on three key components: an accessible source of cells, a suitable biomaterial scaffold, and some combination of biochemical and biomechanical stimulation that makes the tissue grow. There is an added level of complexity in pediatrics, as implanted tissue needs to grow and remodel with the patient.
“A benefit of our approach,” Parvin-Nejad shares, “is our use of readily sourced cells available immediately after birth from the umbilical cord, which would normally be discarded.”
As for the biomaterial, Parvin-Nejad is using a degradable polyurethane developed in the lab of Paul Santerre – another Ted Rogers Centre investigator – to provide the structure and support initially needed by the cells. As the material degrades, it is replaced by the growing tissue until the tissue sheet is comprised exclusively of the patient’s own cells. It is this feature which will allow it to successfully grow and remodel as the patient ages.
Yet before any lab-grown tissue is ready for implant, Parvin-Nejad must evaluate how closely it resembles the native pediatric valve. “We know that pediatric leaflets do not have the same properties as the adult valve,” Parvin-Nejad says. And there are limited sources on this subject that she can turn to for this information. Thus, she is currently establishing new benchmarks, using pig valves to study mechanical behaviour and valve architecture, and plans to use this information to optimize her procedures for biochemical and biomechanical induction of tissue growth.
Collaboration key to reaching the clinic
Collaborators like Dr. Caldarone help ensure this research is on the right path to get to the clinic. “Without this level of collaboration, you might do a lot of good work but it might not be optimal for a clinician.”
Perhaps the greatest asset towards the project’s success is the collaborative environment fostered by the convergence of the clinical and research branches of the Ted Rogers Centre for Heart Research.
“I like that this project is a middle ground between research and clinical work,” Parvin-Nejad says. “I am able to get critical feedback on experiments and designs that are informed by clinical knowledge. What can surgeons do? What can they work with? What is the ideal scenario?”
Still in the early stages of heart valve tissue engineering research, Parvin-Nejad’s work offers promise as an improved solution for children in need of new heart valves.