title: Impact of Cell Composition and Geometry on Human Induced Pluripotent Stem Cells-Derived Engineered Cardiac Tissue.
abstract: The current study describes a scalable, porous large-format engineered cardiac tissue (LF-ECT) composed of human induced pluripotent stem cells (hiPSCs) derived multiple lineage cardiac cells with varied 3D geometries and cell densities developed towards the goal of scale-up for large animal pre-clinical studies. We explored multiple 15 × 15 mm ECT geometries using molds with rectangular internal staggered posts (mesh, ME), without posts (plain sheet, PS), or long parallel posts (multiple linear bundles, ML) and a gel matrix containing hiPSC-derived cardiomyocytes, endothelial, and vascular mural cells matured in vitro for 14 days. ME-ECTs displayed the lowest dead cell ratio (p < 0.001) and matured into 0.5 mm diameter myofiber bundles with greater 3D cell alignment and higher active stress than PS-ECTs. Increased initial ECT cell number beyond 6 M per construct resulted in reduced cell survival and lower active stress. The 6M-ME-ECTs implanted onto 1 week post-infarct immune tolerant rat hearts engrafted, displayed evidence for host vascular coupling, and recovered myocardial structure and function with reduced scar area. We generated a larger (30 × 30 mm) ME-ECT to confirm scalability. Thus, large-format ECTs generated from hiPSC-derived cardiac cells may be feasible for large animal preclinical cardiac regeneration paradigms.
authors.affiliation: Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, The United States of America.|Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.|Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takeichiro
authors.initials: T
authors.lastname: Nakane
authors.affiliation: Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, The United States of America.|Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.|Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Masumoto
authors.affiliation: Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, The United States of America.|Department of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky, The United States of America.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Tinney
authors.affiliation: Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, The United States of America.|Department of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky, The United States of America.
authors.forename: Fangping
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, The United States of America.|Department of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky, The United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Kowalski
authors.affiliation: Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, The United States of America.|Department of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky, The United States of America.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Physiology, University of Louisville, Louisville, Kentucky, The United States of America.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: LeBlanc
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Sakata
authors.affiliation: Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
authors.forename: Jun K
authors.initials: JK
authors.lastname: Yamashita
authors.affiliation: Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, The United States of America.|Department of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky, The United States of America.
authors.forename: Bradley B
authors.initials: BB
authors.lastname: Keller
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D002470:Cell Survival; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000637:transplantation; D011923:Rats, Nude; D012038:Regeneration; D023822:Tissue Engineering / Q000379:methods*; D014183:Transplantation, Heterologous; D020257:Ventricular Remodeling