Division of Cardiology, Inje University Busan Paik Hospital, Busan, Republic of Korea.
Int J Cardiol. 2011 Feb 3;146(3):371-8. doi: 10.1016/j.ijcard.2009.07.016. Epub 2009 Aug 15.
The purpose was to determine whether human adipose-derived stem cells (h-ASCs) can home to the radiofrequency ablated myocardial lesions when injected intravenously and differentiate into cardiomyocyte.
Human adipose tissues were obtained from patients and h-ASCs were isolated and cultured. The phenotype of isolated h-ASCs was identified by flow cytometry. Radiofrequency catheter ablation (RFCA) was performed with ten ablation pulses (40 W, 60 s each) to induce heat-mediated lesions at the free walls of the right atria of 14 dogs. Twenty-four hours after ablation, h-ASCs (1 × 10(7) cells) labeled with superparamagnetic iron oxide particles (SPIOs) were infused intravenously in 10 dogs as cell-therapy group and only saline without cells was infused in 4 dogs as control. The hearts were explanted 4 weeks later.
h-ASCs were identified by flow cytometry as mesenchymal stem cell as positive for CD 13, CD29, CD44, CD90, CD166 and HLA-ABC and immunophenotyping revealed no immunologic responses. SPIO-labeled cells were identified in areas surrounding the RFCA-induced lesions by Prussian blue staining. Immunohistochemistry staining showed positive for anti-α-actinin, anti-cardiac troponin-I, anti-connexin 43 and anti-VEGFR-2. No lymphocyte infiltration, immunorejection or neoplasm-like cells were found in the h-ASC-positive areas. However, multiple iron-labeled h-ASCs were detected in lungs and spleens of cell-therapy group.
h-ASCs can home into injured atrial tissue and express a cardiomyocyte-like phenotype, suggesting that intravenous delivery of stem cells might be feasible. Functional studies and quantification of delivered stem cells are needed for better evaluation and understanding of differentiation into cardiomyocytes.
本研究旨在探讨静脉注射人脂肪干细胞（h-ASCs）是否能归巢至射频消融心肌损伤部位，并分化为心肌细胞。
从患者体内获取脂肪组织，分离并培养 h-ASCs。采用流式细胞术鉴定分离的 h-ASCs 表型。采用射频导管消融（RFCA）在 14 只犬右心房游离壁进行 10 次消融（40 W，每次 60 s），以诱导热介导的损伤。消融后 24 h，将标记有超顺磁性氧化铁颗粒（SPIOs）的 h-ASCs（1×10(7)个细胞）静脉输注至 10 只犬的细胞治疗组，4 只犬仅输注不含细胞的生理盐水作为对照组。4 周后取出心脏。
流式细胞术鉴定 h-ASCs 为间充质干细胞，其 CD13、CD29、CD44、CD90、CD166 和 HLA-ABC 均呈阳性，免疫表型检测未发现免疫反应。普鲁士蓝染色显示，RFCA 诱导损伤部位周围存在 SPIO 标记的细胞。免疫组织化学染色显示抗α-肌动蛋白、抗心肌肌钙蛋白 I、抗连接蛋白 43 和抗 VEGFR-2 阳性。在 h-ASC 阳性区域未发现淋巴细胞浸润、免疫排斥或类肿瘤细胞。然而，在细胞治疗组的肺和脾脏中检测到多个铁标记的 h-ASCs。
h-ASCs 可归巢至损伤的心房组织并表达心肌样表型，提示静脉注射干细胞可能是可行的。需要进行功能研究和对输送干细胞的定量分析，以更好地评估和理解其向心肌细胞的分化。
