Ishida Michiko, Tomita Shinji, Nakatani Takeshi, Fukuhara Shinya, Hamamoto Masaki, Nagaya Noritoshi, Ohtsu Yoshinori, Suga Michiharu, Yutani Chikao, Yagihara Toshikatsu, Yamada Kazuhiko, Kitamura Soichiro
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center, Osaka, Japan.
J Heart Lung Transplant. 2004 Apr;23(4):436-45. doi: 10.1016/S1053-2498(03)00220-1.
Cell transplantation is a promising therapy for treating end-stage heart failure. Bone marrow mononuclear cells (BMMNC) have been used to enhance angiogenesis in ischemic heart disease. However, the effect of BMMNC transplantation in non-ischemic dilated cardiomyopathy is unknown. In this study, we evaluated the efficacy of BMMNC transplantation in doxorubicin-induced cardiomyopathy in a rat model.
Doxorubicin (15 mg/kg, IP) was introduced into 52 Lewis rats. They were divided into 3 groups at 4 weeks after injection: transplant group (TX, BMMNC [1 x 10(6)] implantation, n = 18), control group (CN, saline injection, n = 18), and sham group (SH, thoracotomy, n = 16). At 4 weeks after surgery, we used echocardiography to measure systolic left ventricular diameter (LVDs), diastolic left ventricular diameter (LVDd), fractional shortening (FS), and left ventricular wall thickness/LVDs. We used a Langendorff apparatus to measure systolic, diastolic, and developed pressures. We used radioimmunoassay to measure circulating atrial natriuretic peptide concentration, and we performed histologic study, including electron-microscopic study.
Left ventricular wall thickness/LVDs in the TX group was the largest of all groups (p < 0.05). Systolic and developed pressures in the TX group were the greatest (p < 0.005). Systolic left ventricular diameter, FS, and end-diastolic pressure in the TX group were smaller than in the SH group (p < 0.05). These cardiac parameters did not differ significantly between TX and CN groups, but secondary changes (decreased heart weight, developed ascites, and increased atrial natriuretic peptide concentration) caused by doxorubicin-induced heart failure were most attenuated in the TX group. In the TX group, vascular density was greatest (p < 0.05) in the left ventricular free wall and in the septum. In addition, electron microscopy showed that myocardium in the TX group was most maintained.
Bone marrow mononuclear cell transplantation had beneficial effects in doxorubicin-induced cardiomyopathy.
细胞移植是治疗终末期心力衰竭的一种有前景的疗法。骨髓单个核细胞（BMMNC）已被用于增强缺血性心脏病中的血管生成。然而，BMMNC移植在非缺血性扩张型心肌病中的作用尚不清楚。在本研究中，我们在大鼠模型中评估了BMMNC移植对阿霉素诱导的心肌病的疗效。
将阿霉素（15mg/kg，腹腔注射）注入52只Lewis大鼠体内。注射4周后将它们分为3组：移植组（TX，植入BMMNC[1×10(6)]，n = 18）、对照组（CN，注射生理盐水，n = 18）和假手术组（SH，开胸手术，n = 16）。术后4周，我们使用超声心动图测量左心室收缩直径（LVDs）、舒张直径（LVDd）、缩短分数（FS）以及左心室壁厚度/LVDs。我们使用Langendorff装置测量收缩压、舒张压和舒张末期压力。我们使用放射免疫分析法测量循环心房利钠肽浓度，并进行组织学研究，包括电子显微镜研究。
TX组的左心室壁厚度/LVDs在所有组中最大（p < 0.·05）。TX组的收缩压和舒张末期压力最大（p < 0.·005）。TX组的左心室收缩直径、FS和舒张末期压力小于SH组（p < 0.·05）。这些心脏参数在TX组和CN组之间没有显著差异，但阿霉素诱导的心力衰竭引起的继发性变化（心脏重量减轻、腹水形成和心房利钠肽浓度增加）在TX组中最不明显。在TX组中，左心室游离壁和室间隔的血管密度最大（p < 0.·05）。此外，电子显微镜显示TX组的心肌保存最完好。
骨髓单个核细胞移植对阿霉素诱导的心肌病有有益作用。
