Irradiated cultured apoptotic peripheral blood mononuclear cells regenerate infarcted myocardium.
BACKGROUND
Acute myocardial infarction (AMI) is followed by post AMI cardiac remodelling, often leading to congestive heart failure. Homing of c-kit+ endothelial progenitor cells (EPC) has been thought to be the optimal source for regenerating infarcted myocardium.


METHODS
Immune function of viable peripheral blood mononuclear cells (PBMC) was evaluated after co-culture with irradiated apoptotic PBMC (IA-PBMC) in vitro. Viable PBMC, IA-PBMC and culture supernatants (SN) thereof were obtained after 24 h. Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were utilized to quantify interleukin-8 (IL-8), vascular endothelial growth factor, matrix metalloproteinase-9 (MMP9) in PBMC, SN and SN exposed fibroblasts. Cell suspensions of viable- and IA-PBMC were infused in an experimental rat AMI model. Immunohistological analysis was performed to detect inflammatory and pro-angiogenic cells within 72 h post-infarction. Functional data and determination of infarction size were quantified by echocardiography and Elastica van Gieson staining.


RESULTS
The IA-PBMC attenuated immune reactivity and resulted in secretion of pro-angiogenic IL-8 and MMP9 in vitro. Fibroblasts exposed to viable and IA-PBMC derived SN caused RNA increment of IL-8 and MMP9. AMI rats that were infused with IA-PBMC cell suspension evidenced enhanced homing of endothelial progenitor cells within 72 h as compared to control (medium alone, viable-PBMC). Echocardiography showed a significant reduction in infarction size and improvement in post AMI remodelling as evidenced by an attenuated loss of ejection fraction.


CONCLUSIONS
These data indicate that infusion of IA-PBMC cell suspension in experimental AMI circumvented inflammation, caused preferential homing of regenerative EPC and replaced infarcted myocardium.
Ankersmit
H J
HJ
Department of Surgery, Medical University of Vienna, Vienna, Austria. hendrik.ankersmit@meduniwien.ac.at
Hoetzenecker
K
K
Dietl
W
W
Soleiman
A
A
Horvat
R
R
Wolfsberger
M
M
Gerner
C
C
Hacker
S
S
Mildner
M
M
Moser
B
B
Lichtenauer
M
M
Podesser
B K
BK
D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D009203:Myocardial Infarction / Q000276:immunology / Q000503:physiopathology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016277:Ventricular Function, Left / Q000276:immunology / Q000502:physiology*; D020257:Ventricular Remodeling / Q000276:immunology / Q000502:physiology* / Q000528:radiation effects