title: Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction.
abstract: Cardiac cell therapy suffers from limitations related to poor engraftment and significant cell death after transplantation. In this regard, ex vivo tissue engineering is a tool that has been demonstrated to increase cell retention and survival. The aim of our study was to evaluate the therapeutic potential of a 3D-printed patch composed of human cardiac-derived progenitor cells (hCMPCs) in a hyaluronic acid/gelatin (HA/gel) based matrix. hCMPCs were printed in the HA/gel matrix (30 × 10(6) cells/ml) to form a biocomplex made of six perpendicularly printed layers with a surface of 2 × 2 cm and thickness of 400 μm, in which they retained their viability, proliferation and differentiation capability. The printed biocomplex was transplanted in a mouse model of myocardial infarction (MI). The application of the patch led to a significant reduction in adverse remodeling and preservation of cardiac performance as was shown by both MRI and histology. Furthermore, the matrix supported the long-term in vivo survival and engraftment of hCMPCs, which exhibited a temporal increase in cardiac and vascular differentiation markers over the course of the 4 week follow-up period. Overall, we developed an effective and translational approach to enhance hCMPC delivery and action in the heart.
authors.affiliation: Dept. of Cardiology, DH&L, University Medical Center Utrecht, Utrecht, The Netherlands; Dept. of Molecular Medicine, Cenci-Bolognetti Foundation, Pasteur Institute, "Sapienza" University of Rome, Rome, Italy; Dept. of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, USA. Electronic address: R.gaetani@umcutrecht.nl.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gaetani
authors.affiliation: Dept. of Cardiology, DH&L, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Dries A M
authors.initials: DA
authors.lastname: Feyen
authors.affiliation: Dept. of Cardiology, DH&L, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Vera
authors.initials: V
authors.lastname: Verhage
authors.affiliation: Dept. of Cardiology, DH&L, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rolf
authors.initials: R
authors.lastname: Slaats
authors.affiliation: Dept. of Molecular Medicine, Cenci-Bolognetti Foundation, Pasteur Institute, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Messina
authors.affiliation: Dept. of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Christman
authors.affiliation: Dept. of Molecular Medicine, Cenci-Bolognetti Foundation, Pasteur Institute, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giacomello
authors.affiliation: Dept. of Cardiology, DH&L, University Medical Center Utrecht, Utrecht, The Netherlands; Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands.
authors.forename: Pieter A F M
authors.initials: PA
authors.lastname: Doevendans
authors.affiliation: Dept. of Cardiology, DH&L, University Medical Center Utrecht, Utrecht, The Netherlands; Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands. Electronic address: J.Sluijter@umcutrecht.nl.
authors.forename: Joost P G
authors.initials: JP
authors.lastname: Sluijter
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D051379:Mice; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000637:transplantation*; D010496:Pericardium / Q000473:pathology / Q000503:physiopathology; D066330:Printing, Three-Dimensional; D033581:Stem Cell Transplantation / Q000379:methods*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
chemical_list: D005780:Gelatin; D006820:Hyaluronic Acid
keywords: Cardiac progenitor cells; Cardiac regeneration; Cardiac tissue engineering; Heart failure; Tissue printing