Successful implantation of intravenously administered stem cells correlates with severity of inflammation in murine myocarditis.
The present study was designed to determine whether cardiac inflammation is important for the successful homing of stem cells to the heart after intravenous injection in a murine myocarditis model. Male Bagg albino/c mice were infected with encephalomyocarditis virus (EMCV) to produce myocarditis. Subgroups of mice received single injections by tail vein of embryonic stem cells (ESCs) transfected with green fluorescent protein (GFP) as a marker at days 3, 14, or 60 after infection; other subgroups without stem cell injections were killed at each of these time points to assess the degree of inflammation present. The surviving mice were killed at day 90 after virus infection and hemodynamics, gross pathology, histology, and inflammatory cytokine production in the hearts were measured. Our results indicate that myocardial inflammation was most severe and cytokine production highest at day 14 after EMCV inoculation, and in particular, was strongly positive for interleukin 6. Mice receiving intravenous ESC injections on day 14 after EMCV inoculation showed the largest number of GFP-positive cells at the time of death and the greatest functional improvement compared to uninfected controls without inflammation. We conclude that factors released from myocardium during inflammation are important for enhancing the homing, migration, and implantation of systemically infused stem cells.
Malek
Sohail
S
Charles A. Dana Research Institute and the Harvard-Thorndike Laboratories of Beth Israel Deaconess Medical Center, The Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02135, USA.
Kaplan
Emel
E
Wang
Ju-Feng
JF
Ke
Qingen
Q
Rana
Jamal S
JS
Chen
Yu
Y
Rahim
Bilal G
BG
Li
Ma
M
Huang
Qin
Q
Xiao
Yong-Fu
YF
Verheugt
Freek W A
FW
Morgan
James P
JP
Min
Jiang-Yong
JY
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000502:physiology*; D049452:Green Fluorescent Proteins; D006321:Heart / Q000502:physiology*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D033581:Stem Cell Transplantation / Q000379:methods*
D016207:Cytokines; D049452:Green Fluorescent Proteins