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' lives. 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 optimized xeno-free, good manufacturing practice-compliant culture system. WJ-MSCs were phenotypically and functionally characterized by flow cytometry and multilineage differentiation capacity, respectively. The typical MSC 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. WJ-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 cellularized conduit, engineered with swine WJ-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 pediatric cardiac intervention toward new modalities for effective and personalized surgical restoration of pulmonary artery and RVOT function in TOF/pulmonary atresia patients.

中文翻译：

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沃顿的果冻间充质干细胞工程导管用于心脏缺陷的儿科翻译

可用于法洛四联症（TOF）/肺闭锁患者右心室流出道（RVOT）重建的材料具有长期退化和缺乏生长潜力的严重限制，导致右心室功能障碍、动脉瘤形成和心律失常，因此需要在患者的一生中进行几次高风险的再次手术。在这项研究中，我们评估了源自沃顿氏胶 (WJ-MSCs) 的间充质干细胞 (MSCs)（脐带的凝胶状内部）在我们优化的异种移植物中生长和再细胞化细胞外基质 (ECM) 移植物的能力。 -免费、符合良好生产规范的培养系统。WJ-MSCs 在表型和功能上分别通过流式细胞术和多向分化能力进行表征。典型的 MSC 免疫表型和功能特征保留在我们的无异种培养系统中，以及在天然存在的支架上生长和移植的能力。来自人和猪来源的 WJ-MSCs 显示出出色的再细胞化 ECM 移植物的能力，从而产生活细胞种子构建体。此外，我们还提供了一个用猪 WJ-MSC 设计的细胞化导管的可行性概念的体内证明，可用于主要肺动脉重建的新型猪模型，其中它在宿主组织中显示出良好的整合。我们的研究表明，将 WJ-MSC 添加到 ECM 支架可以升级材料，将其转化为活组织，具有生长、修复和重塑 RVOT 的潜力。这些结果可能代表儿科心脏干预向新模式的范式转变，以有效和个性化地手术恢复 TOF/肺闭锁患者的肺动脉和 RVOT 功能。