Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY, 40202, USA.
Mol Cell Biochem. 2022 Feb;477(2):431-444. doi: 10.1007/s11010-021-04283-2. Epub 2021 Nov 16.
Mounting evidence shows that cell therapy provides therapeutic benefits in experimental and clinical settings of chronic heart failure. However, direct cardiac delivery of cells via transendocardial injection is logistically complex, expensive, entails risks, and is not amenable to multiple dosing. Intravenous administration would be a more convenient and clinically applicable route for cell therapy. Thus, we determined whether intravenous infusion of three widely used cell types improves left ventricular (LV) function and structure and compared their efficacy. Rats with a 30-day-old myocardial infarction (MI) received intravenous infusion of vehicle (PBS) or 1 of 3 types of cells: bone marrow mesenchymal stromal cells (MSCs), cardiac mesenchymal cells (CMCs), and c-kit-positive cardiac cells (CPCs), at a dose of 12 × 10 cells. Rats were followed for 35 days after treatment to determine LV functional status by serial echocardiography and hemodynamic studies. Blood samples were collected for Hemavet analysis to determine inflammatory cell profile. LV ejection fraction (EF) dropped ≥ 20 points in all hearts at 30 days after MI and deteriorated further at 35-day follow-up in the vehicle-treated group. In contrast, deterioration of EF was halted in rats that received MSCs and attenuated in those that received CMCs or CPCs. None of the 3 types of cells significantly altered scar size, myocardial content of collagen or CD45-positive cells, or Hemavet profile. This study demonstrates that a single intravenous administration of 3 types of cells in rats with chronic ischemic cardiomyopathy is effective in attenuating the progressive deterioration in LV function. The extent of LV functional improvement was greatest with CPCs, intermediate with CMCs, and least with MSCs.
越来越多的证据表明,细胞疗法在慢性心力衰竭的实验和临床环境中提供了治疗益处。然而,通过穿壁心肌注射直接向心脏输送细胞在后勤上很复杂、昂贵,并且存在风险,并且不适用于多次给药。静脉内给药将是细胞疗法更方便和更具临床适用性的途径。因此,我们确定了通过静脉内输注三种广泛使用的细胞类型是否可以改善左心室 (LV) 功能和结构,并比较了它们的疗效。患有 30 天陈旧性心肌梗死 (MI) 的大鼠接受了 12×10 个细胞剂量的载体 (PBS) 或 3 种细胞类型中的 1 种的静脉内输注:骨髓间充质基质细胞 (MSCs)、心脏间充质细胞 (CMCs) 和 c-kit 阳性心脏细胞 (CPCs)。在治疗后 35 天对大鼠进行随访,通过连续超声心动图和血流动力学研究确定 LV 功能状态。采集血液样本进行 Hemavet 分析,以确定炎症细胞谱。所有 MI 后 30 天的心脏 LV 射血分数 (EF) 均下降≥20 个点,并且在载体处理组中在 35 天随访时进一步恶化。相比之下,在接受 MSCs 的大鼠中,EF 的恶化得到了阻止,而在接受 CMCs 或 CPCs 的大鼠中则得到了缓解。这 3 种细胞均未显著改变疤痕大小、心肌胶原或 CD45 阳性细胞含量或 Hemavet 谱。这项研究表明,在患有慢性缺血性心肌病的大鼠中单次静脉内给予 3 种细胞可有效减轻 LV 功能的进行性恶化。LV 功能改善程度以 CPCs 最大,CMCs 次之,MSCs 最小。
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