Wharton's Jelly-Mesenchymal Stem Cells- engineered conduit for pediatric translation in Heart Defect.
Tissue engineering. Part A(2020)
Abstract
The materials available for the Right Ventricular Outflow Tract (RVOT) reconstruction in patients with Tetralogy of Fallot (TOF)/pulmonary atresia come with the severe limitation of long-term degeneration and lack of growth potential, causing right ventricular dysfunction, aneurysm formation and arrhythmias, thus necessitating several high-risk reoperations throughout patients' life. In this study, we evaluated the capacity of Mesenchymal Stem Cells (MSCs) derived from the Wharton's Jelly (WJ-MSCs), the gelatinous inner portion of the umbilical cord, to grow and recellularize an extracellular matrix (ECM) graft in our optimised xeno-free, good manufacturing practice- compliant culture system. WJ-MSCs were phenotypically and functionally characterised by flow cytometry and multi-lineage differentiation capacity, respectively. The typical MSCs immunophenotype and functional characteristics were retained in our xeno-free culture system, as well as the capacity to grow and engraft onto a naturally occurring scaffold. Wharton's Jelly MSCs, from both human and swine source, showed excellent capacity to recellularize ECM graft producing a living cell-seeded construct. In addition, we have provided an in vivo proof of concept of feasibility of the cellularised conduit, engineered with swine Wharton's Jelly MSCs, to be used in a novel porcine model of main pulmonary artery reconstruction, where it showed good integration within the host tissue. Our study indicates that the addition of WJ-MSCs to the ECM scaffold can upgrade the material, converting it into a living tissue, with the potential to grow, repair and remodel the RVOT. These results could potentially represent a paradigm shift in paediatric cardiac intervention towards new modalities for effective and personalised surgical restoration of pulmonary artery and RVOT function in TOF/pulmonary atresia patients.
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Key words
congenital heart disease, right ventricular outflow tract reconstruction, stem cells, swine model, tissue engineering
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