Fibroblast sheets co-cultured with endothelial progenitor cells improve cardiac function of infarcted hearts

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• 作者：Hiroshi Kobayashi ; Tatsuya Shimizu ; Masayuki Yamato ; Kayoko Tono ; Haruchika Masuda ; Takayuki Asahara ; Hiroshi Kasanuki and Teruo Okano
• 关键词：Tissue engineering ; Cell sheet ; Endothelial progenitor cells ; Heart
• 刊名：Journal of Artificial Organs
• 出版年：2008
• 出版时间：September, 2008
• 年：2008
• 卷：11
• 期：3
• 页码：141-147
• 全文大小：373.1 KB

文摘

We have already confirmed that cell sheet transplantation can improve damaged heart function via continuous cytokine secretion. In this study, we hypothesized that cytokine-secreting cell sheets co-cultured with an endothelial cell source may be more effective for repairing ischemic myocardium. Confluent rat fibroblasts cultured on temperature-responsive culture dishes were harvested as contiguous cell sheets by temperature reduction. Green fluorescent protein (GFP)-positive endothelial progenitor cells (EPCs) were seeded on fibroblast sheets to create co-cultured cell sheets, and sandwich-like constructs were engineered by stacking of the co-cultured cell sheets. These constructs were transplanted into rat myocardial infarction models. Cardiac function and histology were assessed in four groups: the sham operation (C) group, the isolated EPC injection (E) group, the transplantation of triple-layer fibroblast sheets (F) group, and the transplantation of triple-layer sandwich-like constructs (E + F) group. Echocardiography showed significant improvement of the fractional shortening in the E + F group in comparison with the C group (0.25 ¡À 0.05 vs. 0.16 ¡À 0.02). On histological examination, significantly less connective tissue formation was observed in the E, F, and E + F groups when compared to the C group (C, E, F, and E + F groups: 53 ¡À 2 % , 41 ¡À 4 % , 40 ¡À 4 % , and 32 ¡À 7 % , respectively). Additionally, increased blood vessel formation was detected in the E, F, and E + F groups compared with the C group (C, E, F, and E + F groups: 1.9 % ¡À 0.6 % , 6.7 % ¡À 0.6 % , 7.8 % ¡À 0.9 % , and 10.2 % ¡À 2.4 % , respectively). Furthermore, GFP-staining demonstrated that the newly formed blood vessels were composed of the co-cultured EPCs. Transplantation of cell sheets co-cultured with an endothelial cell source may be a new therapeutic strategy for myocardial tissue regeneration.