The real estate of myoblast cardiac transplantation: Negative remodeling is associated with location
The real estate of myoblast cardiac transplantation: Negative remodeling is associated with location
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DOI：
10.1016/j.healun.2007.10.011
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发表时间：
2008-01-01
影响因子：
8.9
通讯作者：
Taylor, Doris A.
中科院分区：
文献类型：
--
作者：
McCue, Jonathan D.;Swingen, Cory;Taylor, Doris A.
背景：骨骼肌成肌细胞移植被认为是一种治疗缺血性心肌病的方法，因为它可能在肌肉生成中发挥作用。基于瘢痕内位置的相对安全性和有效性尚不清楚。我们推测骨骼肌成肌细胞移植到外周瘢痕(与中央瘢痕相比)可以更有效地减轻负性左心室(LV)重构，但存在心律失常的风险。方法：新西兰大白兔(n=34)结扎左前降支(LAD)中段造成跨壁左室梗死。LAD结扎1个月后，分别在瘢痕中心(n=13)和瘢痕周围(n=10)注射成肌细胞，并与注射生理盐水(n=11)进行比较。注射前进行Holter监测和磁共振成像(MRI)；注射后2周继续进行Holter监测，1个月时进行MRI随访。结果：中央处理组动物的左心室收缩末期容量、舒张期末容量和质量增加，并与注射的细胞数量相关。与载体相比，接受外周处理的动物的负性左心室重构有减弱的趋势。在几个中心注射的动物中发现了明显的晚期异位，而在外周注射的动物中没有观察到晚期异位。结论：我们注意到中心注射后负性左室重构的不良反应，提示移植细胞相对于瘢痕的位置可能是骨骼肌成肌细胞心脏移植安全性和有效性的关键因素。骨骼肌成肌细胞注射到周围瘢痕中似乎是安全的，与假注射相比，有改善功能的趋势。
Background: Skeletal myoblast transplantation has been proposed as a therapy for ischemic cardiomyopathy owing to its possible role in myogenesis. The relative safety and efficacy based on location within scar is not known. We hypothesized that skeletal myoblasts transplanted into peripheral scar (compared with central scar) would more effectively attenuate negative left ventricular (LV) remodeling but at the risk of arrhythmia.Methods: New Zealand White rabbits (n = 34) underwent mid-left anterior descending artery (LAD) ligation to produce a transmural LV infarction. One month after LAD ligation, skeletal myoblasts were injected either in the scar center (n = 13) or scar periphery (n = 10) and compared with saline injection (n = 11). Holter monitoring and magnetic resonance imaging (MRI) was performed pre-injection; Holter monitoring was continued until 2 weeks after injection, with follow-up MRI at 1 month.Results: The centrally treated animals demonstrated increased LV end-systolic volume, end-diastolic volume, and mass that correlated with the number of injected cells. There was a trend toward attenuation of negative LV remodeling in peripherally treated animals compared with vehicle. Significant late ectopy was seen in several centrally injected animals, with no late ectopy seen in peripherally injected animals.Conclusions: We noted untoward effects with respect to negative LV remodeling after central injection, suggesting that transplanted cell location with respect to scar may be a key factor in the safety and efficacy of skeletal myoblast cardiac transplantation. Administration of skeletal myoblasts into peripheral scar appears safe, with a trend toward improved function in comparison with sham injection.