Microvessel co-transplantation improves poor remuscularization by hiPSC-cardiomyocytes in a complex disease model of myocardial infarction and type 2 diabetes.

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Stem Cell Reports Pub Date : 2025-02-11 Epub Date: 2025-01-23 DOI:10.1016/j.stemcr.2024.102394
Xuetao Sun, Jun Wu, Omar Mourad, Renke Li, Sara S Nunes
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Abstract

People with type 2 diabetes (T2D) are at a higher risk for myocardial infarction (MI) than age-matched healthy individuals. Here, we studied cell-based cardiac regeneration post MI in T2D rats modeling the co-morbid conditions in patients with MI. We recapitulated the T2D hallmarks and clinical aspects of diabetic cardiomyopathy using high-fat diet and streptozotocin in athymic rats, which were then subjected to MI and intramyocardial implantation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with or without rat adipose-derived microvessels (MVs). hiPSC-CM alone engrafted poorly. Co-delivery of hiPSC-CMs with MVs yielded a smaller infarct area and a thicker left ventricle wall. Additionally, MVs robustly integrated into the infarcted hearts, improved the survival of hiPSC-CMs, and improved cardiac function. MV-conditioned media also promoted hiPSC-CM maturation in vitro, increasing cardiomyocyte (CM) size in an interleukin (IL)-6-dependent manner. Given the availability of MVs from human adipose tissue, MVs present great translational potential for the treatment of heart failure in people with T2D.

微血管共移植改善了hipsc -心肌细胞在心肌梗死和2型糖尿病复杂疾病模型中的再肌化不良。
2型糖尿病(T2D)患者发生心肌梗死(MI)的风险高于年龄匹配的健康人。在这里,我们研究了心肌梗死后T2D大鼠的基于细胞的心脏再生,模拟了心肌梗死患者的合并症。我们在胸腺大鼠中使用高脂肪饮食和链ptozocin概述了糖尿病心肌病的T2D特征和临床方面,然后对心肌梗死和人诱导多能干细胞来源的心肌细胞(hiPSC-CMs)进行心肌内植入,其中有或没有大鼠脂肪来源的微血管(mv)。hiPSC-CM单独移植效果较差。hiPSC-CMs与mv的共同递送产生较小的梗死面积和较厚的左心室壁。此外,MVs可以稳定地融入梗死心脏,提高hiPSC-CMs的存活率,并改善心功能。mv条件培养基也促进hiPSC-CM体外成熟,以白细胞介素(IL)-6依赖的方式增加心肌细胞(CM)的大小。鉴于人体脂肪组织中mv的可用性,mv在治疗t2dm患者心力衰竭方面具有巨大的转化潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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