Enhanced cell transplantation: preventing apoptosis increases cell survival and ventricular function
Enhanced cell transplantation: preventing apoptosis increases cell survival and ventricular function
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DOI：
10.1152/ajpheart.00155.2006
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发表时间：
2006-08-01
影响因子：
4.8
通讯作者：
Li, Ren-Ke
中科院分区：
文献类型：
--
作者：
Nakamura, Yoshinobu;Yasuda, Tamotsu;Li, Ren-Ke
细胞移植可预防心肌梗塞后的心脏功能障碍。然而，由于大多数植入细胞因缺血和凋亡而丢失，因此可以通过提高细胞存活率来改善细胞移植对心脏功能的益处。为了检验这种可能性，用抗凋亡 Bcl-2 基因转染或热休克对雄性 Lewis 大鼠主动脉平滑肌细胞 (SMC；4 x 10(6)) 进行预处理，然后植入麻醉的同源雌性大鼠的梗死心肌中（每组 n = 23 只）。移植后第一天，使用转移酶介导的 dUTP 缺口末端标记染色对凋亡的 SMC 进行定量。在第 7 天和第 28 天，使用实时 PCR 定量移植细胞存活率，并使用超声心动图和 Langendorff 装置评估心脏功能。相对于对照组，接受抗凋亡预处理的 SMC 在每项指标上均表现出改善。相对于所有其他组，Bcl-2 处理的细胞凋亡减少 (P < 0.05)，而存活率增加 (P < 0.01)。相对于对照组，热休克还显着减少细胞凋亡并增加存活率（组效应 P < 0.05），尽管这些效应不如 Bcl-2 治疗组明显。此外，与对照组相比，Bcl-2 治疗组和热休克治疗组的疤痕面积均减少（P < 0.05），并且面积变化分数和心脏功能更大（两项测量均 P < 0.05）。这些结果表明，抗凋亡预处理减少了移植后移植的 SMC 损失，增强了移植细胞的存活和心室功能，这与存活的移植细胞的数量直接相关（r = 0.72；P = 0.002）。
Cell transplantation prevents cardiac dysfunction after myocardial infarction. However, because most implanted cells are lost to ischemia and apoptosis, the benefits of cell transplantation on heart function could be improved by increasing cell survival. To examine this possibility, male Lewis rat aortic smooth muscle cells (SMCs; 4 x 10(6)) were pretreated with antiapoptotic Bcl-2 gene transfection or heat shock and then implanted into the infarcted myocardium of anesthetized, syngenic female rats (n = 23 per group). On the first day after transplantation, apoptotic SMCs were quantified by using transferase-mediated dUTP nick-end labeling staining. On days 7 and 28, grafted cell survival was quantified by using real-time PCR, and heart function was assessed with the use of echocardiography and the Langendorff apparatus. SMCs given antiapoptotic pretreatments exhibited improvements in each measure relative to controls. Apoptosis was reduced in Bcl-2-treated cells relative to all other groups (P < 0.05), whereas survival (P < 0.01) was increased. Heat shock also significantly decreased apoptosis and increased survival relative to control groups (P < 0.05 for group effect), although these effects were less pronounced than in the Bcl-2-treated group. Further, scar areas were reduced in both Bcl-2- and heat shock-treated groups relative to controls (P < 0.05), and fractional area change and cardiac function were greater (P < 0.05 for both measures). These results indicate that antiapoptosis pretreatments reduced grafted SMC loss after transplantation and enhanced grafted cell survival and ventricular function, which was directly related (r = 0.72; P = 0.002) to the number of surviving engrafted cells.