Guijarro D, Lebrin M, Lairez O, Bourin P, Piriou N, Pozzo J, Lande G, Berry M, Le Tourneau T, Cussac D, Sensebe L, Gross F, Lamirault G, Huynh A, Manrique A, Ruidavet J B, Elbaz M, Trochu J N, Parini A, Kramer S, Galinier M, Lemarchand P, Roncalli J
INSERM, UMR1087, l'institut du thorax, CNRS, UMR6291, Université de Nantes, CHU de Nantes, Nantes F-44000, France.
Department of Cardiology, Institute CARDIOMET, PCVM, University of Toulouse, CHU de Toulouse, France; Clinical Center of Investigation of Biotherapy, CIC, CHU Toulouse, France.
Int J Cardiol. 2016 Apr 15;209:258-65. doi: 10.1016/j.ijcard.2016.02.016. Epub 2016 Feb 2.
The MESAMI 1 trial was a bicentric pilot study designed to test the feasibility and safety of intramyocardially injected autologous bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of ischemic cardiomyopathy.
The study included 10 patients with chronic myocardial ischemia, left ventricular (LV) ejection fractions (EFs) of ≤35%, and reversible perfusion defects who were on stable optimal medical therapy and were not candidates for revascularization. MSCs (mean: 61.5×10(6) cells per patient) were injected into 10-16 viable sites at the border of the LV scar via a NOGA-guided catheter. Both primary endpoints, feasibility (successful harvest, expansion, and injection of autologous MSCs) and safety (absence of severe adverse events [SAEs]) were met in all 10 patients at the 1-month follow-up time point, and none of the SAEs reported during the full 2-year follow-up period were attributable to the study intervention. The results of secondary efficacy endpoint analyses identified significant improvements from baseline to Month 12 in LVEF (29.4±2.0% versus 35.7±2.5%; p=0.003), LV end-systolic volume (167.8±18.8mL versus 156.1±28.6mL; p=0.04), 6-min walk test and NYHA functional class.
Our results suggest that autologous MSCs can be safely administered to the hearts of patients with severe, chronic, reversible myocardial ischemia and impaired cardiac function and may be associated with improvements in cardiac performance, LV remodeling, and patient functional status. A randomized, double blind, multicenter, placebo-controlled clinical trial (MESAMI 2) will evaluate the efficacy of this treatment approach in a larger patient population.
Unique identifier: NCT01076920.
MESAMI 1试验是一项双中心试点研究，旨在测试经心肌内注射自体骨髓间充质基质细胞（MSC）治疗缺血性心肌病的可行性和安全性。
该研究纳入了10例慢性心肌缺血患者，这些患者左心室（LV）射血分数（EF）≤35%，存在可逆性灌注缺损，接受稳定的最佳药物治疗且不适合进行血运重建。通过NOGA引导导管将MSC（平均每位患者61.5×10⁶个细胞）注射到LV瘢痕边界的10 - 16个存活部位。在1个月的随访时间点，所有10例患者均达到了两个主要终点，即可行性（成功采集、扩增和注射自体MSC）和安全性（无严重不良事件[SAE]），并且在整个2年随访期内报告的SAE均与研究干预无关。次要疗效终点分析结果显示，从基线到第12个月，LVEF（29.4±2.0%对35.7±2.5%；p = 0.003）、LV收缩末期容积（167.8±18.8mL对156.1±28.6mL；p = 0.04）、6分钟步行试验和纽约心脏协会（NYHA）功能分级均有显著改善。
我们的结果表明，自体MSC可以安全地施用于患有严重、慢性、可逆性心肌缺血和心功能受损的患者心脏，并且可能与心脏功能、LV重塑和患者功能状态的改善有关。一项随机、双盲、多中心、安慰剂对照的临床试验（MESAMI 2）将在更大的患者群体中评估这种治疗方法的疗效。
唯一标识符：NCT01076920。
