title: Gelatin Microspheres as Vehicle for Cardiac Progenitor Cells Delivery to the Myocardium.
abstract: Inadequate cell retention and survival in cardiac stem cell therapy seems to be reducing the therapeutic effect of the injected stem cells. In order to ameliorate their regenerative effects, various biomaterials are being investigated for their potential supportive properties. Here, gelatin microspheres (MS) are utilized as microcarriers to improve the delivery and therapeutic efficacy of cardiac progenitor cells (CPCs) in the ischemic myocardium. The gelatin MS, generated from a water-in-oil emulsion, are able to accommodate the attachment of CPCs, thereby maintaining their cardiogenic potential. In a mouse model of myocardial infarction, we demonstrated the ability of these microcarriers to substantially enhance cell engraftment in the myocardium as indicated by bioluminescent imaging and histological analysis. However, despite an observed tenfold increase in CPC numbers in the myocardium, echocardiography, and histology reveals that mice treated with MS-CPCs show marginal improvement in cardiac function compared to CPCs only. Overall, a straightforward and translational approach is developed to increase the retention of stem cells in the ischemic myocardium. Even though the current biomaterial setup with CPCs as cell source does not translate into improved therapeutic action, coupling this developed technology with stem cell-derived cardiomyocytes can lead to an effective remuscularization therapy.
authors.affiliation: Department of Cardiology, DH&L, University Medical Center Utrecht, Utrecht 3584, CX, The Netherlands.
authors.forename: Dries A M
authors.initials: DA
authors.lastname: Feyen
authors.affiliation: Department of Cardiology, DH&L, University Medical Center Utrecht, Utrecht 3584, CX, The Netherlands.|Department of Molecular Medicine, Cenci-Bolognetti Foundation, Pasteur Institute, "Sapienza" University of Rome, 00161, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gaetani
authors.affiliation: Department of Cardiology, DH&L, University Medical Center Utrecht, Utrecht 3584, CX, The Netherlands.
authors.forename: Janine
authors.initials: J
authors.lastname: Deddens
authors.affiliation: Department of Cardiology, DH&L, University Medical Center Utrecht, Utrecht 3584, CX, The Netherlands.
authors.forename: Danielle
authors.initials: D
authors.lastname: van Keulen
authors.affiliation: Department of Cardiology, DH&L, University Medical Center Utrecht, Utrecht 3584, CX, The Netherlands.
authors.forename: Chantal
authors.initials: C
authors.lastname: van Opbergen
authors.affiliation: Department of Orthopedics, University Medical Center Utrecht, Utrecht 3584, CX, The Netherlands.
authors.forename: Michelle
authors.initials: M
authors.lastname: Poldervaart
authors.affiliation: Department of Orthopedics, University Medical Center Utrecht, Utrecht 3584, CX, The Netherlands.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Alblas
authors.affiliation: Department of Cardiology, DH&L, University Medical Center Utrecht, Utrecht 3584, CX, The Netherlands.
authors.forename: Steven
authors.initials: S
authors.lastname: Chamuleau
authors.affiliation: Department of Cardiology, DH&L, University Medical Center Utrecht, Utrecht 3584, CX, The Netherlands.
authors.forename: Linda W
authors.initials: LW
authors.lastname: van Laake
authors.affiliation: Department of Cardiology, DH&L, University Medical Center Utrecht, Utrecht 3584, CX, The Netherlands.|Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht 3511, EP, The Netherlands.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.affiliation: Department of Cardiology, DH&L, University Medical Center Utrecht, Utrecht 3584, CX, The Netherlands.|Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht 3511, EP, The Netherlands.|Department of Cardiology, DH&L, University Medical Center Utrecht, Experimental Cardiology Laboratory, Heidelberglaan 100, Room G03.642, Utrecht 3584, CX, The Netherlands.
authors.forename: Joost P G
authors.initials: JP
authors.lastname: Sluijter
mesh_terms: D000818:Animals; D018914:Cells, Immobilized / Q000378:metabolism / Q000637:transplantation; D004195:Disease Models, Animal; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008863:Microspheres; D032386:Myoblasts, Cardiac / Q000378:metabolism / Q000637:transplantation; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology
chemical_list: D005780:Gelatin
keywords: biomaterials; cardiac progenitor cells; cell therapy; delivery; engraftment; microspheres