Schmuck Eric G, Koch Jill M, Hacker Timothy A, Hatt Charles R, Tomkowiak Michael T, Vigen Karl K, Hendren Nicholas, Leitzke Cathlyn, Zhao Ying-Qi, Li Zhanhai, Centanni John M, Hei Derek J, Schwahn Denise, Kim Jaehyup, Hematti Peiman, Raval Amish N
Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Division of Cardiovascular Medicine, Department of Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, H4/568 Clinical Sciences Center, 600 Highland Ave, Madison, WI, 53792-3248, USA.
J Cardiovasc Transl Res. 2015 Oct;8(7):438-48. doi: 10.1007/s12265-015-9654-0. Epub 2015 Sep 15.
The aim of this study is to determine the effects of early intravenous (IV) infusion later followed by transendocardial (TE) injection of allogeneic mesenchymal stem cells (MSCs) following myocardial infarction (MI). Twenty-four swine underwent balloon occlusion reperfusion MI and were randomized into 4 groups: IV MSC (or placebo) infusion (post-MI day 2) and TE MSC (or placebo) injection targeting the infarct border with 2D X-ray fluoroscopy fused to 3D magnetic resonance (XFM) co-registration (post-MI day 14). Continuous ECG recording, MRI, and invasive pressure-volume analyses were performed. IV MSC plus TE MSC treated group was superior to other groups for contractility reserve (p = 0.02) and freedom from VT (p = 0.03) but had more lymphocytic foci localized to the peri-infarct region (p = 0.002). No differences were observed in post-MI remodeling parameters. IV followed by XFM targeted TE MSC therapy improves contractility reserve and suppresses VT but does not affect post-MI remodeling and may cause an immune response.
本研究的目的是确定心肌梗死(MI)后早期静脉注射(IV)随后经心内膜(TE)注射同种异体间充质干细胞(MSC)的效果。24只猪接受球囊闭塞再灌注心肌梗死,并随机分为4组:静脉注射MSC(或安慰剂)(心肌梗死后第2天),并在二维X线透视与三维磁共振融合(XFM)共配准下经心内膜注射MSC(或安慰剂)靶向梗死边缘(心肌梗死后第14天)。进行连续心电图记录、磁共振成像和有创压力-容积分析。静脉注射MSC加经心内膜注射MSC治疗组在收缩储备(p = 0.02)和无室性心动过速(VT)方面优于其他组(p = 0.03),但梗死周边区域有更多淋巴细胞灶(p = 0.002)。在心肌梗死后重塑参数方面未观察到差异。静脉注射后经XFM靶向的经心内膜MSC治疗可改善收缩储备并抑制室性心动过速,但不影响心肌梗死后重塑,且可能引起免疫反应。