title: Fate of modular cardiac tissue constructs in a syngeneic rat model.
abstract: Modular cardiac tissues developed both vascular and cardiac structures in vivo, provided that the host response was attenuated by omitting xenoproteins from the modules. Collagen gel modules (with Matrigel(TM)) containing cardiomyocytes (CMs) alone or CMs with surface-seeded endothelial cells (ECs; CM/EC modules) were injected into the peri-infarct zone of the heart in syngeneic Lewis rats. After 3 weeks, donor ECs developed into blood vessel-like structures that also contained erythrocytes. However, no donor CMs were found within the implant sites, presumably because host cells including macrophages and T cells infiltrated extensively into the injection sites. To lessen the host response, Matrigel was omitted from the matrix and the modules were rinsed with serum-free medium prior to implantation. Host cell infiltration was attenuated, resulting in a higher degree of vascularization with CM/EC modules than with CM modules without ECs. Most importantly, donor CMs matured into striated muscle-like structures in Matrigel-free implants.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Ontario, Canada.
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Leung
authors.affiliation: Toronto General Research Institute, Division of Cardiovascular Surgery, University Health Network and University of Toronto, Ontario, Canada.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyagi
authors.affiliation: Toronto General Research Institute, Division of Cardiovascular Surgery, University Health Network and University of Toronto, Ontario, Canada.|Divison of Experimental Therapeutics, Toronto General Research Institute (TGRI), Ontario, Canada.
authors.forename: Ren-Ke
authors.initials: RK
authors.lastname: Li
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Ontario, Canada.|Department of Chemical Engineering and Applied Chemistry, University of Toronto, Ontario, Canada.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sefton
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry*; D016895:Culture Media, Serum-Free / Q000737:chemistry; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology; D004912:Erythrocytes / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000737:chemistry; D020007:Implants, Experimental; D007797:Laminin / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism; D008856:Microscopy, Fluorescence; D032383:Myocytes, Cardiac / Q000166:cytology*; D018919:Neovascularization, Physiologic; D011509:Proteoglycans / Q000737:chemistry*; D051381:Rats; D011917:Rats, Inbred Lew; D055647:Rats, Transgenic; D023822:Tissue Engineering / Q000379:methods*; D014185:Transplantation, Isogeneic
chemical_list: D016895:Culture Media, Serum-Free; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D049452:Green Fluorescent Proteins; D003094:Collagen
keywords: angiogenesis; cardiac tissue; endothelial cells; in vivo model; modular constructs; tissue remodelling