McCue Jonathan D, Swingen Cory, Feldberg Tanya, Caron Gabe, Kolb Adam, Denucci Christopher, Prabhu Somnath, Motilall Randy, Breviu Brian, Taylor Doris A
Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
J Heart Lung Transplant. 2008 Jan;27(1):116-23. doi: 10.1016/j.healun.2007.10.011.
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.
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.
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.
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.
由于骨骼肌成肌细胞在肌生成中可能发挥的作用，其已被提议作为缺血性心肌病的一种治疗方法。基于瘢痕内位置的相对安全性和有效性尚不清楚。我们假设，与移植到中央瘢痕相比，移植到外周瘢痕的骨骼肌成肌细胞能更有效地减轻左心室（LV）负性重构，但存在心律失常的风险。
34只新西兰白兔接受左前降支（LAD）中段结扎以产生透壁性左心室梗死。LAD结扎1个月后，将骨骼肌成肌细胞注射到瘢痕中心（n = 13）或瘢痕外周（n = 10），并与注射生理盐水的动物（n = 11）进行比较。在注射前进行动态心电图监测和磁共振成像（MRI）；动态心电图监测持续至注射后2周，1个月后进行随访MRI。
接受中央注射治疗的动物左心室收缩末期容积、舒张末期容积和质量增加，且与注射细胞数量相关。与注射生理盐水的动物相比，接受外周注射治疗的动物左心室负性重构有减轻趋势。在几只接受中央注射的动物中观察到明显的晚期异位心律，而接受外周注射的动物未观察到晚期异位心律。
我们注意到中央注射后左心室负性重构存在不良影响，这表明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。将骨骼肌成肌细胞注射到外周瘢痕似乎是安全的，与假注射相比有功能改善的趋势。
