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Irradiated cultured apoptotic peripheral blood mononuclear cells regenerate infarcted myocardium
Author(s) -
Ankersmit H. J.,
Hoetzenecker K.,
Dietl W.,
Soleiman A.,
Horvat R.,
Wolfsberger M.,
Gerner C.,
Hacker S.,
Mildner M.,
Moser B.,
Lichtenauer M.,
Podesser B. K.
Publication year - 2009
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2009.02111.x
Subject(s) - peripheral blood mononuclear cell , immune system , medicine , immunology , progenitor cell , biology , in vitro , stem cell , microbiology and biotechnology , biochemistry
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. Conclusion 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.