Homing of intravenously infused embryonic stem cell-derived cells to injured hearts after myocardial infarction.
OBJECTIVE
The present study was designed to test whether intravenously infused embryonic stem cell-derived cells could translocate to injured myocardium after myocardial infarction and improve cardiac function.


METHODS
Cultured embryonic stem cell-derived cells were transfected with green fluorescent protein. Embryonic stem cell-derived cells were administered through the tail vein (approximately 10(7) cells in 1 mL of medium for each rat) every other day for 6 days in 45 rats after myocardial infarction. Six weeks after myocardial infarction and cell infusion, cardiac function, blood flow, and the numeric density of arterioles were measured to test the benefits of cell therapy. An in vitro Transwell assay was performed to evaluate the embryonic stem cell migration.


RESULTS
Ventricular function, regional blood flow, and arteriole density were significantly increased in rats receiving intravenously infused embryonic stem cell-derived cells compared with control rats after myocardial infarction. Histologic analysis demonstrated that infused embryonic stem cell-derived cells formed green fluorescent protein-positive grafts in infarcted myocardium. Additionally, positive immunostaining for cardiac troponin I was found in hearts after myocardial infarction receiving embryonic stem cell-derived cell infusion that corresponded to the green fluorescent protein-positive staining. The Transwell migration assay indicated that cultured neonatal rat cardiomyocytes with overexpression of tumor necrosis factor alpha induced greater migration of embryonic stem cells compared with cardiomyocytes without tumor necrosis factor alpha expression.


CONCLUSIONS
Our data demonstrate that intravenously infused embryonic stem cell-derived cells homed to the infarcted heart, improved cardiac function, and enhanced regional blood flow at 6 weeks after myocardial infarction. The in vitro migration assay suggested that such a homing mechanism could be associated with locally released cytokines, such as tumor necrosis factor alpha, that are upregulated in the setting of acute myocardial infarction and heart failure.
Min
Jiang-Yong
JY
Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass, USA.
Huang
Xuling
X
Xiang
Meixiang
M
Meissner
Achim
A
Chen
Yu
Y
Ke
Qingen
Q
Kaplan
Emel
E
Rana
Jamal S
JS
Oettgen
Peter
P
Morgan
James P
JP
D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D049452:Green Fluorescent Proteins; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha; D016277:Ventricular Function, Left
D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins