Strategies Affording Prevascularized Cell-Based Constructs for Myocardial Tissue Engineering

Table 1

Strategies to promote functional vascularization of cardiac patches.

Cell source/vascular explants	Scaffold/cell sheets	Bioreactors/other devices	Biological effects	Ref.
hESC-derived cardiomyocytes; /HUVECs/MEFs	Porous scaffold	None	Formation of both donor and host-derived vasculature within the engrafted triculture tissue constructs	[11]
hESC-derived cardiomyocytes; /HUVECs/MEFs; /human dermal fibroblasts	None	Rotating orbital shaker	Contraction of constructs in response to electrical pacing up to frequencies of 2-3 Hz/formation of new blood vessels in rat myocardium	[12]
HUVECs	Collagen	Intact microvascular segments gelled in polyethylene tubes	Formation of patent vascularized structures in the infarcted mouse heart/increase in cardiac contractility	[13]
Neonatal rat cardiac cells	Alginate plus angiogenic factors	Inosculation from heterotopic rat omentum of microvessels within the construct	Structural and electrical integration of cardiac patch into the infarcted rat myocardium/induction of thicker scars/prevention of chamber dilatation and ventricular dysfunction	[14]
Mouse cardiac tissues, thoracic artery, vena cava/rat and human arteries and veins/neonatal rat cardiomyocytes	Thymosin β4-releasing hydrogel scaffold	Polydimethylsiloxane substrate with grooves produced through soft lithography	In vitro improved functional properties of the cardiac construct/cell striations/cell-cell junctions/guided capillary outgrowths	[15]
HUVECs/human skeletal myoblasts	Cell sheets	HUVECs sandwiched between sheets of myoblasts	Cell sheets sprouted a capillary-like network and efficiently connected to the host vessels	[16]
HUVECs	Poly(ethylene glycol)-diacrylate hydrogel scaffold	Device micropatterned with cell-adhesive ligands by photolithography	Spatial regulation of the angiogenic response	[17]
Human microvascular endothelial cells/human dermal fibroblasts	Collagen	System for guided tubulogenesis coupled with 3D organotypic culture	Endothelial tube formation/endothelial vessels surrounded by collagen type IV	[18]
Neonatal rat cardiomyocytes/transduced mouse skeletal myoblasts releasing VEGF	Porous poly(glycerol sebacate) scaffold	Channels produced by a CO2 computerized laser	Formation of a geometrically ordered mature vascular network in mouse infarcted myocardium	[19]
Rat MSCs/HUVECs	Decellularized porcine heart tissue	None	Preservation of macro- and micro-vascular architecture and ultrastructure of native cardiac tissue	[20]
Human microvascular endothelial cells	Collagen or poly-D-lysine-hydrobromide	Microfluidic device	Gradients in channeled scaffolds create high-throughput angiogenesis	[21]
Rat MSCs	Hyaluronan	Unidirectional cyclic stretch bioreactor	Cell multilayer organization and invasion of the 3D mesh of the scaffold/muscle protein expression	[22]
HUVECs	Alginate	Multishear perfusion bioreactor	Expression of the intercellular adhesion molecule 1 (ICAM-1) and the phosphorylated endothelial nitric oxide synthase (eNOS)	[23]
Mouse endothelial cell line (MS-1)	Polycaprolactone porous scaffold	Shear perfusion bioreactor	Rapid endothelialization method to create preformed artificial vascular; networks in scaffolds	[24]
Neonatal rat cardiac cells/rat endothelial cells	Cell sheets	Perfusion bioreactor	In vivo transplantation of a thick vascularized beating cardiac tissue	[25]
hESCs/hiPSCs/HUVECs/hMSCs	Collagen	Uniaxial stress bioreactor (FlexCell FX-4000T)	Cardiomyocyte and matrix fiber alignment/myofibrillogenesis and sarcomeric banding/increased vessel-like structures	[26]