title: Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult.
abstract: A main challenge in cardiac tissue engineering is the limited data on microenvironmental cues that sustain survival, proliferation and functional proficiency of cardiac cells. The aim of our study was to evaluate the potential of fetal (E18) and adult myocardial extracellular matrix (ECM) to support cardiac cells. Acellular three-dimensional (3D) bioscaffolds were obtained by parallel decellularization of fetal- and adult-heart explants thereby ensuring reliable comparison. Acellular scaffolds retained main constituents of the cardiac ECM including distinctive biochemical and structural meshwork features of the native equivalents. In vitro, fetal and adult ECM-matrices supported 3D culture of heart-derived Sca-1(+) progenitors and of neonatal cardiomyocytes, which migrated toward the center of the scaffold and displayed elongated morphology and excellent viability. At the culture end-point, more Sca-1(+) cells and cardiomyocytes were found adhered and inside fetal bioscaffolds, compared to the adult. Higher repopulation yields of Sca-1(+) cells on fetal ECM relied on β1-integrin independent mitogenic signals. Sca-1(+) cells on fetal bioscaffolds showed a gene expression profile that anticipates the synthesis of a permissive microenvironment for cardiomyogenesis. Our findings demonstrate the superior potential of the 3D fetal microenvironment to support and instruct cardiac cells. This knowledge should be integrated in the design of next-generation biomimetic materials for heart repair.
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto 4200-135, Portugal; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto 4050-313, Portugal; Gladstone Institutes, University of California San Francisco, San Francisco 94158, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Silva
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto 4200-135, Portugal.
authors.forename: S C
authors.initials: SC
authors.lastname: Rodrigues
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto 4200-135, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Caldeira
authors.affiliation: Centre for Ecology, Evolution and Environmental Change, Departamento de Biologia Animal, Faculdade de Ciências, Universidade de Lisboa, Lisboa 1749-016, Portugal.
authors.forename: A M
authors.initials: AM
authors.lastname: Nunes
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto 4200-135, Portugal; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto 4050-313, Portugal.
authors.forename: V
authors.initials: V
authors.lastname: Sampaio-Pinto
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto 4200-135, Portugal.
authors.forename: T P
authors.initials: TP
authors.lastname: Resende
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto 4200-135, Portugal; Faculty of Medicine, University of Porto, Porto 4200-319, Portugal.
authors.forename: M J
authors.initials: MJ
authors.lastname: Oliveira
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto 4200-135, Portugal; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto 4050-313, Portugal.
authors.forename: M A
authors.initials: MA
authors.lastname: Barbosa
authors.affiliation: Centre for Ecology, Evolution and Environmental Change, Departamento de Biologia Animal, Faculdade de Ciências, Universidade de Lisboa, Lisboa 1749-016, Portugal.
authors.forename: S
authors.initials: S
authors.lastname: Thorsteinsdóttir
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto 4200-135, Portugal. Electronic address: dsn@ineb.up.pt.
authors.forename: D S
authors.initials: DS
authors.lastname: Nascimento
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto 4200-135, Portugal; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto 4050-313, Portugal; Unit for Lymphopoiesis, Immunology Department, INSERM U668, University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur. Institut Pasteur, Paris, France. Electronic address: perpetua@ineb.up.pt.
authors.forename: P
authors.initials: P
authors.lastname: Pinto-do-Ó
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002474:Cell-Free System / Q000737:chemistry; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry*; D005240:Feasibility Studies; D005318:Fetal Heart / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*; D066330:Printing, Three-Dimensional; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D054457:Tissue Scaffolds
keywords: 3D scaffolds; Cardiac tissue engineering; Decellularization; Extracellular matrix; Fetal microenvironments