title: Tissue-transplant fusion and vascularization of myocardial microtissues and macrotissues implanted into chicken embryos and rats.
abstract: Cell-based therapies and tissue engineering initiatives are gathering clinical momentum for next-generation treatment of tissue deficiencies. By using gravity-enforced self-assembly of monodispersed primary cells, we have produced adult and neonatal rat cardiomyocyte-based myocardial microtissues that could optionally be vascularized following coating with human umbilical vein endothelial cells (HUVECs). Within myocardial microtissues, individual cardiomyocytes showed native-like cell shape and structure, and established electrochemical coupling via intercalated disks. This resulted in the coordinated beating of microtissues, which was recorded by means of a multi-electrode complementary metal-oxide-semiconductor microchip. Myocardial microtissues (microm3 scale), coated with HUVECs and cast in a custom-shaped agarose mold, assembled to coherent macrotissues (mm3 scale), characterized by an extensive capillary network with typical vessel ultrastructures. Following implantation into chicken embryos, myocardial microtissues recruited the embryo's capillaries to functionally vascularize the rat-derived tissue implant. Similarly, transplantation of rat myocardial microtissues into the pericardium of adult rats resulted in time-dependent integration of myocardial microtissues and co-alignment of implanted and host cardiomyocytes within 7 days. Myocardial microtissues and custom-shaped macrotissues produced by cellular self-assembly exemplify the potential of artificial tissue implants for regenerative medicine.
authors.affiliation: Institute for Chemical and Bio-Engineering, Swiss Federal Institute of Technology, Zurich, Switzerland.
authors.forename: Jens M
authors.initials: JM
authors.lastname: Kelm
authors.forename: Valentin
authors.initials: V
authors.lastname: Djonov
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hoerstrup
authors.forename: Christina I
authors.initials: CI
authors.lastname: Guenter
authors.forename: Lars M
authors.initials: LM
authors.lastname: Ittner
authors.forename: Frauke
authors.initials: F
authors.lastname: Greve
authors.forename: Andreas
authors.initials: A
authors.lastname: Hierlemann
authors.forename: Carlota Diaz
authors.initials: CD
authors.lastname: Sanchez-Bustamante
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Perriard
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ehler
authors.forename: Martin
authors.initials: M
authors.lastname: Fussenegger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001705:Bioprosthesis; D002478:Cells, Cultured; D002642:Chick Embryo; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure; D006801:Humans; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic; D051381:Rats; D017208:Rats, Wistar; D023822:Tissue Engineering / Q000379:methods; D016378:Tissue Transplantation / Q000379:methods; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous; D019737:Transplants