쥐 심근경색 모델에서 이식된 인간 양막 상피세포에서 전혈관형성 싸이토카인의 paracrine 효과

Abstract

ABSTRACT Paracrine effect of secreted pro-angiogenic cytokine from transplanted human amniotic epithelial cells in rat model of myocardial infarction

Yi-Sun Song Department of Translational Medicine, Graduate School of Biomedical Science & Engineering, Hanyang University

Background: Human amniotic epithelial cells (h-AECs) have been shown to differentiate into cardiomyocyte-like cells in vivo and regenerate myocardial tissue to improve cardiac function in a rat model of myocardial infarction (MI). However, the role of paracrine factors in h-AECs mediated cardiac repair in a rat model of MI remains unclear. Methods and Results: This study investigated whether paracrine factors are released from h-AECs under hypoxic conditions and whether these factors are expressed in h-AECs-treated tissues in a rat model of MI. Exposure of h-AECs to hypoxia (0% O2) for up to 24 h caused an increase in the expression of hypoxia-induced factor (HIF)-1α compared to that seen in h-AECs in normoxic conditions (21% O2). An antibody-based protein array and ELISA analyses of h-AECs-conditioned medium indicated that h-AECs secreted greater amounts of cytokines, including angiogenin (ANG), epidermal growth factor (EGF), interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 under hypoxic conditions compared to expression under normoxic conditions. The MI model was generated by ligation of the left anterior descending (LAD) coronary artery of the rats. After the ligation, rats were injected with h-AECs or saline into the MI areas. To confirm the survival of h-AECs in the infarct region by 1 day and 1 week after transplantation, the present study performed immunofluorescence analysis. In addition, using reverse transcription-polymerase chain reaction, h-AECs-treated rats showed greater expression of the human-origin cytokines ANG, EGF, IL-6, and MCP-1 in the infarct and border zone compared to expression in the saline-treated rats. Conclusion: Taken together, this study indicates that the effects of h-AECs treatment in a rat model of MI are associated with paracrine effects of human cytokines derived from h-AECs such as ANG, EGC, IL-6 and MCP-1.