Viable fibroblast matrix patch induces angiogenesis and increases myocardial blood flow in heart failure after myocardial infarction.
BACKGROUND
This study examines a viable biodegradable three-dimensional fibroblast construct (3DFC) in a model of chronic heart failure. The viable fibroblasts, cultured on a vicryl mesh, secrete growth factors that stimulate angiogenesis.


METHODS
We ligated the left coronary artery of male Sprague-Dawley rats, implanted the 3DFC 3 weeks after myocardial infarction and obtained end point data 3 weeks later, that is, 6 weeks after myocardial infarction.


RESULTS
Implanting the 3DFC increases (p<0.05) myocardial blood flow twofold, microvessel formation (0.02±0.01 vs. 0.07±0.03 vessels/μm2), and ventricular wall thickness (0.53±0.02 to 1.02±0.17mm). The 3DFC shifts the passive pressure volume loop toward the pressure axis but does not alter left ventricular (LV) ejection fraction, systolic displacement, LV end-diastolic pressure/dimension, or LV cavity area. The 3DFC stimulates selected cytokine activation with a decrease in the proinflammatory cascade and increased total protein content stimulated by strained 3DFC in vitro.


CONCLUSIONS
The 3DFC functions as a cell delivery device providing matrix support for resident cell survival and integration into the heart. The imbedded fibroblasts of the 3DFC release a complex blend of cardioactive cytokines promoting increases in microvessel density and anterior wall blood flow but does not improve ejection fraction or alter LV remodeling.
Lancaster
Jordan
J
Department of Cardiology, Southern Arizona VA HealthCare System, Tucson, Arizona 85723, USA.
Juneman
Elizabeth
E
Hagerty
Tracy
T
Do
Rose
R
Hicks
Michael
M
Meltzer
Kate
K
Standley
Paul
P
Gaballa
Mohamed
M
Kellar
Robert
R
Goldman
Steven
S
Thai
Hoang
H
D000818:Animals; D001696:Biomechanical Phenomena; D003326:Coronary Circulation / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004452:Echocardiography; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D006333:Heart Failure / Q000628:therapy*; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*
D016207:Cytokines