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Institute for Regenerative Medicine • IREM

New publication of Fioretta et al. in JACC: Basic to Translational Science.

Differential Leaflet Remodeling of Bone Marrow Cell Pre-Seeded Versus Nonseeded Bioresorbable Transcatheter Pulmonary Valve Replacements

Initially developed for inoperable and high-risk patients, transcatheter valve replacement (TVR) procedures have been recently extended also to intermediate- and low-risk patients. Currently, only stented heart valve bioprostheses are compatible with minimally-invasive TVR techniques. However, these prostheses are susceptible to progressive degeneration and calcification, which impact valve durability. Tissue engineered heart valves (TEHVs) based on bioresorbable polymers with in situ regenerative potential may solve this problem by transforming into a living valve after implantation. In this study, we investigated the effect of bone marrow mononuclear cell (BMMNC) pre-seeding on bioresorbable bis-urea-modified polycarbonate (PC-BU) TEHVs. In a one-step pre-implantation procedure, we seeded autologous BMMNCs onto PC-BU TEHVs and evaluated functionality and remodeling over 24 weeks. When compared to non-seeded TEHVs, BMMNC pre-seeding had detrimental effects on tissue remodeling and valve performance. Independent of pre-seeding, heterogeneous valve and leaflet remodeling were observed. Our findings suggest that BMMNC pre-seeding does not improve TEHV remodeling and that further studies should investigate the causes of the observed leaflet-dependent remodeling mechanisms to increase the safety profile of the valves, before achieving a clinically relevant valve replacement solution. by Emanuela S. Fioretta, Valentina Lintas, Anna Mallone, Sarah E. Motta, Lisa von Boehmer, Petra E. Dijkman, Nikola Cesarovic, Etem Caliskan, Héctor Rodriguez Cetina Biefer, Miriam Lipiski, Mareike Sauer, Matilde Putti, Henk M.Janssen, Serge H.Söntjens, Anthal I.P.M.Smits, Carlijn V.C.Bouten, Maximilian Y. Emmert, Simon P. Hoerstrup