Dib Nabil, Campbell Ann, Jacoby Douglas B, Zawadzka Agatha, Ratliff Judson, Miedzybrocki Brigitte M, Gahremanpour Amir, Diethrich Edward B, Opie Shaun R
Arizona Heart Institute, Phoenix, USA.
J Pharmacol Toxicol Methods. 2006 Jul-Aug;54(1):71-7. doi: 10.1016/j.vascn.2005.12.002. Epub 2006 Feb 3.
Autologous skeletal myoblast transplantation (ASMT) for myocardial regeneration is a promising new treatment for patients with congestive heart failure secondary to myocardial infarction (MI). However, non-surgical delivery could broaden the utility of this approach. The present study was designed to evaluate the safety and feasibility of transplanting autologous skeletal myoblast (ASM) via endovascular delivery into the infarcted swine myocardium.
Seven female Yorkshire swine successfully underwent induced left ventricular MI. ASM biopsies were obtained from the hind limb of each animal and myoblasts were expanded in vitro. In a pilot experiment, ASM were labeled with iridium and short-term retention and biodistribution was determined 2 h after ASM delivery via the MyoStar needle-injection catheter inserted through the femoral artery. At 30 days post-infarction, the remaining animals were divided into three groups containing 2 animals each for percutaneous catheter delivery into the infarcted zone: group 1 control animals were injected with media only, group 2 and 3 animals were injected with approximately 300 x 10(6) and 600 x 10(6) ASM, respectively. Sixty days post-transplantation, the swine hearts were harvested.
During the 60-day period between transplantation and harvest, no adverse events were recorded, and continuous rhythm monitoring revealed no arrhythmias. In the small sampling size, myocardial function assessments revealed a trend toward improvement in the treatment groups with respect to ejection fraction, viability, and cardiac index. However, histology of treated swine hearts identified no skeletal muscle cells.
Percutaneous ASMT into an infarcted swine myocardium is feasible and safe, and may contribute to overall improved heart function.
自体骨骼肌成肌细胞移植（ASMT）用于心肌再生是治疗心肌梗死（MI）继发充血性心力衰竭患者的一种有前景的新疗法。然而，非手术递送可扩大该方法的应用范围。本研究旨在评估通过血管内递送将自体骨骼肌成肌细胞（ASM）移植到梗死猪心肌中的安全性和可行性。
七只雌性约克夏猪成功诱导发生左心室心肌梗死。从每只动物的后肢获取ASM活检组织，并在体外扩增成肌细胞。在一项先导实验中，用铱标记ASM，并在通过经股动脉插入的MyoStar针注射导管递送ASM后2小时测定其短期滞留和生物分布。在心肌梗死后30天，将其余动物分为三组，每组2只，经皮导管递送至梗死区域：第1组为对照动物，仅注射培养基，第2组和第3组动物分别注射约300×10⁶和600×10⁶个ASM。移植后60天，收获猪心脏。
在移植至收获的60天期间，未记录到不良事件，连续心律监测未发现心律失常。在小样本量中，心肌功能评估显示治疗组在射血分数、生存能力和心脏指数方面有改善趋势。然而，经治疗的猪心脏组织学检查未发现骨骼肌细胞。
经皮将ASM移植到梗死猪心肌中是可行且安全的，可能有助于整体改善心脏功能。
