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2017 ; 7
(1
): 4566
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English Wikipedia
Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human
Induced Pluripotent Stem Cell Derived Cardiomyocytes
#MMPMID28676704
Ong CS
; Fukunishi T
; Zhang H
; Huang CY
; Nashed A
; Blazeski A
; DiSilvestre D
; Vricella L
; Conte J
; Tung L
; Tomaselli GF
; Hibino N
Sci Rep
2017[Jul]; 7
(1
): 4566
PMID28676704
show ga
We have developed a novel method to deliver stem cells using 3D bioprinted
cardiac patches, free of biomaterials. Human induced pluripotent stem
cell-derived cardiomyocytes (hiPSC-CMs), fibroblasts (FB) and endothelial cells
(EC) were aggregated to create mixed cell spheroids. Cardiac patches were created
from spheroids (CM:FB:EC?=?70:15:15, 70:0:30, 45:40:15) using a 3D bioprinter.
Cardiac patches were analyzed with light and video microscopy,
immunohistochemistry, immunofluorescence, cell viability assays and optical
electrical mapping. Cardiac tissue patches of all cell ratios beat spontaneously
after 3D bioprinting. Patches exhibited ventricular-like action potential
waveforms and uniform electrical conduction throughout the patch. Conduction
velocities were higher and action potential durations were significantly longer
in patches containing a lower percentage of FBs. Immunohistochemistry revealed
staining for CM, FB and EC markers, with rudimentary CD31+ blood vessel
formation. Immunofluorescence revealed the presence of Cx43, the main cardiac gap
junction protein, localized to cell-cell borders. In vivo implantation suggests
vascularization of 3D bioprinted cardiac patches with engraftment into native rat
myocardium. This constitutes a significant step towards a new generation of stem
cell-based treatment for heart failure.