P346Transplantation of hTERT-Immortalized mASCs and HUVECs into infarcted rat myocardium improved cardiac function and induced expression of inflammatory cytokines

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Purpose: Adipose stem cells evoke only minimal immune reactivity and cooperate with endothelial progenitor cells to promote and stabilize new vessel formation. Mouse ASCs (mASCs), HUVECs, and mASCs combined with HUVECs were transplanted into acute myocardial infarction (AMI) rats to investigate their synergistic roles on inflammation reaction and regeneration of infarcted myocardium.

Methods: mASCs were immortalized by infecting with retroviruses harboring the hTERT-IRES eGFP gene. AMI rats were divided into 4 groups; Control, mASCs, HUVECs and mASCs+HUVECs groups (n=15, respectively), and 5 X 105 cells per rat were transplanted into rat AMI model. Echocardiographic examinations, peripheral blood cytokine analysis and real-time PCR analysis were performed after cell transplantation.

Results : The immortalized mASCs expressed CD29, CD44, CD106 and Sca-1, and represented multi-differentiation potential. Significant improvements in ejection fraction value were observed in the mASCs, HUVECs and mASC+HUVECs injection groups (P=0.034, 0.030, 0.032, respectively) compared with the control group at 4 week after cell transplantation. Plasma MCP-1 and IL-6 levels significantly decreased in a cell-type specific manner. MCP-1 mRNAs significantly increased in the HUVECs and mASCs+HUVECs injection group at 1 and 2 weeks after cell transplantation. TNF-α mRNAs significantly increased in the mASCs and mASCs+HUVECs injection group at 1 day and the mASCs+HUVECs injection group at 1 week after cell transplantation. IL-10 mRNAs significantly increased in the mASCs and mASCs+HUVECs injection group at 1 and 2 weeks, and the mASCs+HUVECs injection group at 4 weeks after cell transplantation.

Conclusions: Transplantation of mASCs and HUVECs into rat infarcted myocardium improved cardiac function, but induced expressions of inflammatory cytokines in a cell type-specific manner. Synergistic effect in both mASCs and HUVECs injection group was not found.

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