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

Emanuela S. Fioretta, PhD; Valentina Lintas, PhD; Anna Mallone, PhD; Sarah E. Motta, PhD; Lisa von Boehmer, DVM; Petra E. Dijkman, PhD; Nikola Cesarovic, DVM, PhD; Etem Caliskan, MD; Héctor Rodriguez Cetina Biefer, MD; Miriam Lipiski, DVM; Mareike Sauer, DVM; Matilde Putti, PhD; Henk M. Janssen, PhD; Serge H. Söntjens, PhD; Anthal I.P.M. Smits, PhD; Carlijn V.C. Bouten, PhD; Maximilian Y. Emmert, MD, PhD; Simon P. Hoerstrup, MD, PhD

JACC: Basic to Translational Science (Jan 2020)

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

Emanuela S. Fioretta, PhD,
Valentina Lintas, PhD,
Anna Mallone, PhD,
Sarah E. Motta, PhD,
Lisa von Boehmer, DVM,
Petra E. Dijkman, PhD,
Nikola Cesarovic, DVM, PhD,
Etem Caliskan, MD,
Héctor Rodriguez Cetina Biefer, MD,
Miriam Lipiski, DVM,
Mareike Sauer, DVM,
Matilde Putti, PhD,
Henk M. Janssen, PhD,
Serge H. Söntjens, PhD,
Anthal I.P.M. Smits, PhD,
Carlijn V.C. Bouten, PhD,
Maximilian Y. Emmert, MD, PhD,
Simon P. Hoerstrup, MD, PhD

Affiliations

Emanuela S. Fioretta, PhD: Institute for Regenerative Medicine, University of Zürich, Zürich, Switzerland
Valentina Lintas, PhD: Institute for Regenerative Medicine, University of Zürich, Zürich, Switzerland; Wyss Translational Center Zürich, University of Zürich and ETH Zürich, Zürich, Switzerland
Anna Mallone, PhD: Institute for Regenerative Medicine, University of Zürich, Zürich, Switzerland
Sarah E. Motta, PhD: Institute for Regenerative Medicine, University of Zürich, Zürich, Switzerland
Lisa von Boehmer, DVM: Institute for Regenerative Medicine, University of Zürich, Zürich, Switzerland
Petra E. Dijkman, PhD: Institute for Regenerative Medicine, University of Zürich, Zürich, Switzerland
Nikola Cesarovic, DVM, PhD: Division of Surgical Research, University of Zürich, Zürich, Switzerland; Department of Cardiovascular Surgery, University Hospital Zürich, Zürich, Switzerland
Etem Caliskan, MD: Department of Cardiovascular Surgery, Charité Universitätsmedizin Berlin, Berlin, Germany; Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Berlin, Germany
Héctor Rodriguez Cetina Biefer, MD: Department of Cardiovascular Surgery, University Hospital Zürich, Zürich, Switzerland
Miriam Lipiski, DVM: Division of Surgical Research, University of Zürich, Zürich, Switzerland
Mareike Sauer, DVM: Division of Surgical Research, University of Zürich, Zürich, Switzerland
Matilde Putti, PhD: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands
Henk M. Janssen, PhD: SyMO-Chem B.V., Eindhoven, the Netherlands
Serge H. Söntjens, PhD: SyMO-Chem B.V., Eindhoven, the Netherlands
Anthal I.P.M. Smits, PhD: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands
Carlijn V.C. Bouten, PhD: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands
Maximilian Y. Emmert, MD, PhD: Institute for Regenerative Medicine, University of Zürich, Zürich, Switzerland; Wyss Translational Center Zürich, University of Zürich and ETH Zürich, Zürich, Switzerland; Department of Cardiovascular Surgery, Charité Universitätsmedizin Berlin, Berlin, Germany; Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Berlin, Germany; Address for correspondence: Dr. Maximilian Y. Emmert, Institute for Regenerative Medicine, Moussonstrasse 13, 8044 Zürich, Switzerland.
Simon P. Hoerstrup, MD, PhD: Institute for Regenerative Medicine, University of Zürich, Zürich, Switzerland; Wyss Translational Center Zürich, University of Zürich and ETH Zürich, Zürich, Switzerland; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Dr. Simon P. Hoerstrup, Institute for Regenerative Medicine, Moussonstrasse 13, 8044 Zürich, Switzerland.

Journal volume & issue: Vol. 5, no. 1
pp. 15 – 31

Abstract

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Summary: This study showed that bone marrow mononuclear cell pre-seeding had detrimental effects on functionality and in situ remodeling of bioresorbable bisurea-modified polycarbonate (PC-BU)-based tissue-engineered heart valves (TEHVs) used as transcatheter pulmonary valve replacement in sheep. We also showed heterogeneous valve and leaflet remodeling, which affects PC-BU TEHV safety, challenging their potential for clinical translation. We suggest that bone marrow mononuclear cell pre-seeding should not be used in combination with PC-BU TEHVs. A better understanding of cell–scaffold interaction and in situ remodeling processes is needed to improve transcatheter valve design and polymer absorption rates for a safe and clinically relevant translation of this approach. Key Words: cardiovascular regenerative medicine, endogenous tissue regeneration, in situ tissue engineering, supramolecular polymer, tissue-engineered heart valve

Published in JACC: Basic to Translational Science

ISSN: 2452-302X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.journals.elsevier.com/jacc-basic-to-translational-science/

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