Human amniotic epithelial cells (h-AECs) have been shown to differentiate into cardiomyocyte-like cells in vivo that can regenerate myocardial tissue and improve cardiac function in a rat model of myocardial infarction (MI). In this study, we investigated the paracrine factors released from h-AECs under hypoxic conditions to elucidate the possible mechanisms underlying this previously reported phenomenon of h-AEC-mediated cardiac repair. We used hypoxic cell culture conditions to simulate myocardial infarction in vitro. In comparison to normal conditions, we found that h-AECs secreted higher levels of several cytokines, including angiogenin (ANG), epidermal growth factor (EGF), interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. To determine whether transplanted h-AECs express these proangiogenic cytokines in vivo, we ligated the coronary artery of rats to cause MI and injected either h-AECs or saline into the infarcted area. We found that the infarct and border zones of rat myocardium treated with h-AECs had higher expression levels of the humanorigin cytokines ANG, EGF, IL-6, and MCP-1 compared to the tissues of saline-treated rats. In conclusion, h-AECs secreted proangiogenic cytokines in a rat model of MI, which may suggest that the paracrine effect by h-AECs could regenerate myocardial tissue and improve cardiac function.

Bone marrow-mesenchymal stem cell (BM-MSC) therapy improves the recovery of cardiac function after myocardial infarction (MI); however, the underlying molecular mechanisms are not completely understood. Recent studies have shown that microRNAs (miRNAs) modulate the pathophysiology of cardiovascular diseases. Here, we investigated the mechanisms underlying the effects of BM-MSC-derived paracrine factors and cardiac miRNAs on myocardial regeneration after MI. In our study, MI was induced by permanent ligation of the left anterior descending (LAD) coronary artery. BM-MSCs transplanted in infarcted rats significantly downregulated the expression of miRNA-23a and miRNA-92a and inhibited apoptosis in the myocardium. An in vitro experiment showed that supernatant from BM-MSCs cultured under hypoxia contained higher levels of vascular endothelial growth factor (VEGF) than that from BM-MSCs under normoxia. In addition, inhibition of miRNA-23a and miRNA-92a reduced cardiac apoptosis. Moreover, the VEGF-containing BM-MSC supernatant inhibited miRNA-23a and miRNA-92a expression and reduced apoptotic signaling in cardiomyocytes under hypoxia. These effects were inhibited when the supernatant was treated with neutralizing antibodies against VEGF. Our results indicate that the paracrine factor, VEGF, derived from transplanted BM-MSCs, regulated the expression of miRNAs such as miRNA-23a and miRNA-92a and exerted anti-apoptotic effects in cardiomyocytes after MI.

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The skin functions as a protective barrier against the environment. Loss of the integrity of large areas of skin may lead to increased risk of illness [1]. Wound healing is essential to prevent invasion of pathogens and to maintain the integrity of normal tissue [2], and involves several steps including inflammation, formation of granulation tissue, remodeling of connective tissue, collagenization, and formation of new blood vessels [3]. Granulocyte-colony stimulating factor (G-CSF) directly stimulates neutrophil-restricted progenitor cells into proliferation and differentiation [4]. It has been reported to be effective in the treatment of tissue repair in post-myocardial infarction by enhancing mobilization of neutrophils and macrophages from bone marrow [5]. Recently, Wang et al. [6] demonstrated that systemic injection of G-CSF can accelerate wound healing in mice. They suggested that G-CSF repairs wounds through mobilization of bone marrow derived cells (BMDCs) and up-regulation of growth factors. Recent findings, however, have indicated that G-CSF acts directly on cardiomyocytes and monocytes by binding to a receptor expressed on these cells [7-9]. Moreover, Mueller et al. [10] reported that keratinocyte express G-CSF receptors (G-CSFR). The therapeutic effects of local injection of G-CSF on wound healing in a rat wound model remain unclear. In this study, we investigated whether local injection of G-CSF can accelerate wound healing in a rat wound model, and evaluated whether the effects of local injection of G-CSF on wound healing occurred faster than that those of systemic injection. We also investigated the presence of G-CSFRs in wound tissues. MATERIALS AND METHODS Animals Male Sprague-Dawley rats (Koatech, Pyeongtaek, Korea), 10 weeks of age and weighing 280-300 g, were used. The rats were

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