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

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

doi:10.1016/j.jacbts.2019.09.008

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

JACC Basic Transl Sci. 2019 Dec 11;5(1):15-31. doi: 10.1016/j.jacbts.2019.09.008. eCollection 2020 Jan.

Authors

Emanuela S Fioretta¹, Valentina Lintas^{1

2}, Anna Mallone¹, Sarah E Motta¹, Lisa von Boehmer¹, Petra E Dijkman¹, Nikola Cesarovic^{3

4}, Etem Caliskan^{5

6}, Héctor Rodriguez Cetina Biefer⁴, Miriam Lipiski³, Mareike Sauer³, Matilde Putti^{7

8}, Henk M Janssen⁹, Serge H Söntjens⁹, Anthal I P M Smits^{7

8}, Carlijn V C Bouten^{7

8}, Maximilian Y Emmert^{1

2

5

6}, Simon P Hoerstrup^{1

2

7}

Affiliations

¹ Institute for Regenerative Medicine, University of Zürich, Zürich, Switzerland.
² Wyss Translational Center Zürich, University of Zürich and ETH Zürich, Zürich, Switzerland.
³ Division of Surgical Research, University of Zürich, Zürich, Switzerland.
⁴ Department of Cardiovascular Surgery, University Hospital Zürich, Zürich, Switzerland.
⁵ Department of Cardiovascular Surgery, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁶ Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Berlin, Germany.
⁷ Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
⁸ Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands.
⁹ SyMO-Chem B.V., Eindhoven, the Netherlands.

Abstract

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.

Keywords: B-GLAP, bone gamma-carboxyglutamate; BMMNC, bone marrow mononuclear cells; BVG, bioresorbable vascular graft; CXCL12, stromal cell-derived factor-1α (SDF1α); ECM, extracellular matrix; IL, interleukin; MCP, monocyte chemoattractant protein; MMP, matrix metalloproteinase; PC-BU, polycarbonate bisurea; SMA, smooth muscle actin; TEE, transesophageal echocardiography; TEHV, tissue-engineered heart valve; TGF, transforming growth factor; TVR, transcatheter valve replacement; cardiovascular regenerative medicine; endogenous tissue regeneration; in situ tissue engineering; supramolecular polymer; tissue-engineered heart valve.