人胚胎干细胞衍生的内皮细胞产物注射可减轻心肌梗死中的心脏重塑。
Human embryonic stem cell-derived endothelial cell product injection attenuates cardiac remodeling in myocardial infarction.
作者信息
Spiroski Ana-Mishel, McCracken Ian R, Thomson Adrian, Magalhaes-Pinto Marlene, Lalwani Mukesh K, Newton Kathryn J, Miller Eileen, Bénézech Cecile, Hadoke Patrick, Brittan Mairi, Mountford Joanne C, Beqqali Abdelaziz, Gray Gillian A, Baker Andrew H
机构信息
Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
BHF Centre for Vascular Regeneration, University of Edinburgh, Edinburgh, United Kingdom.
出版信息
Front Cardiovasc Med. 2022 Oct 10;9:953211. doi: 10.3389/fcvm.2022.953211. eCollection 2022.
BACKGROUND
Mechanisms contributing to tissue remodeling of the infarcted heart following cell-based therapy remain elusive. While cell-based interventions have the potential to influence the cardiac healing process, there is little direct evidence of preservation of functional myocardium.
AIM
The aim of the study was to investigate tissue remodeling in the infarcted heart following human embryonic stem cell-derived endothelial cell product (hESC-ECP) therapy.
MATERIALS AND METHODS
Following coronary artery ligation (CAL) to induce cardiac ischemia, we investigated infarct size at 1 day post-injection in media-injected controls (CALM, = 11), hESC-ECP-injected mice (CALC, = 10), and dead hESC-ECP-injected mice (CALD, = 6); echocardiography-based functional outcomes 14 days post-injection in experimental (CALM, = 13; CALC, = 17) and SHAM surgical mice ( = 4); and mature infarct size (CALM and CALC, both = 6). We investigated ligand-receptor interactions (LRIs) in hESC-ECP cell populations, incorporating a publicly available C57BL/6J mouse cardiomyocyte-free scRNAseq dataset with naive, 1 day, and 3 days post-CAL hearts.
RESULTS
Human embryonic stem cell-derived endothelial cell product injection reduces the infarct area (CALM: 54.5 ± 5.0%, CALC: 21.3 ± 4.9%), and end-diastolic (CALM: 87.8 ± 8.9 uL, CALC: 63.3 ± 2.7 uL) and end-systolic ventricular volume (CALM: 56.4 ± 9.3 uL, CALC: 33.7 ± 2.6 uL). LRI analyses indicate an alternative immunomodulatory effect mediated viable hESC-ECP-resident signaling.
CONCLUSION
Delivery of the live hESC-ECP following CAL modulates the wound healing response during acute pathological remodeling, reducing infarct area, and preserving functional myocardium in this relatively acute model. Potential intrinsic myocardial cellular/hESC-ECP interactions indicate that discreet immunomodulation could provide novel therapeutic avenues to improve cardiac outcomes following myocardial infarction.
背景
基于细胞的治疗后梗死心脏组织重塑的机制仍不清楚。虽然基于细胞的干预措施有可能影响心脏愈合过程，但几乎没有直接证据表明功能性心肌得以保留。
目的
本研究旨在调查人胚胎干细胞衍生的内皮细胞产物（hESC-ECP）治疗后梗死心脏的组织重塑情况。
材料与方法
在冠状动脉结扎（CAL）诱导心脏缺血后，我们调查了注射培养基的对照组（CALM，n = 11）、注射hESC-ECP的小鼠（CALC，n = 10）和注射死亡hESC-ECP的小鼠（CALD，n = 6）在注射后1天的梗死面积；在注射后14天对实验组（CALM，n = 13；CALC，n = 17）和假手术小鼠（n = 4）进行基于超声心动图的功能评估；以及成熟梗死面积（CALM和CALC，均为n = 6）。我们利用公开可用的C57BL/6J小鼠无心肌细胞scRNAseq数据集，结合CAL术后第0天、第1天和第3天的心脏，研究了hESC-ECP细胞群体中的配体-受体相互作用（LRI）。
结果
注射人胚胎干细胞衍生的内皮细胞产物可减小梗死面积（CALM：54.5±5.0%，CALC：21.3±4.9%），以及舒张末期（CALM：87.8±8.9μL；CALC：63.3±2.7μL）和收缩末期心室容积（CALM：56.4±9.3μL；CALC：33.7±2.6μL）。LRI分析表明，存活的hESC-ECP驻留信号介导了一种替代性免疫调节作用。
结论
在CAL后递送活的hESC-ECP可调节急性病理重塑过程中的伤口愈合反应，减小梗死面积，并在这个相对急性的模型中保留功能性心肌。潜在的内在心肌细胞/hESC-ECP相互作用表明，谨慎地进行免疫调节可为改善心肌梗死后的心脏结局提供新的治疗途径。
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