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可注射胶原支架通过长期局部保留移植的人脐带间充质干细胞促进猪心肌梗死的恢复。

Injectable collagen scaffold promotes swine myocardial infarction recovery by long-term local retention of transplanted human umbilical cord mesenchymal stem cells.

机构信息

Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.

Center for Clinical Stem Cell Research, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.

出版信息

Sci China Life Sci. 2021 Feb;64(2):269-281. doi: 10.1007/s11427-019-1575-x. Epub 2020 Jul 23.

DOI:10.1007/s11427-019-1575-x
PMID:32712833
Abstract

Stem cell therapy is an attractive approach for recovery from myocardial infarction (MI) but faces the challenges of rapid diffusion and poor survival after transplantation. Here we developed an injectable collagen scaffold to promote the long-term retention of transplanted cells in chronic MI. Forty-five minipigs underwent left anterior descending artery (LAD) ligation and were equally divided into three groups 2 months later (collagen scaffold loading with human umbilical mesenchymal stem cell (hUMSC) group, hUMSC group, and placebo group (only phosphate-buffered saline (PBS) injection)). Immunofluorescence staining indicated that the retention of transplanted cells was promoted by the collagen scaffold. Echocardiography and cardiac magnetic resonance imaging (CMR) showed much higher left ventricular ejection fraction (LVEF) and lower infarct size percentage in the collagen/hUMSC group than in the hUMSC and placebo groups at 12 months after treatment. There were also higher densities of vWf-, α-sma-, and cTnT-positive cells in the infarct border zone in the collagen/cell group, as revealed by immunohistochemical analysis, suggesting better angiogenesis and more cardiomyocyte survival after MI. Thus, the injectable collagen scaffold was safe and effective on a large animal myocardial model, which is beneficial for constructing a favorable microenvironment for applying stem cells in clinical MI.

摘要

干细胞疗法是心肌梗死(MI)康复的一种有吸引力的方法,但面临着移植后快速扩散和存活率低的挑战。在这里,我们开发了一种可注射的胶原支架,以促进移植细胞在慢性 MI 中的长期保留。45 只小型猪进行了左前降支(LAD)结扎,2 个月后平均分为三组(胶原支架负载人脐带间充质干细胞(hUMSC)组、hUMSC 组和安慰剂组(仅注射磷酸盐缓冲盐水(PBS)))。免疫荧光染色表明胶原支架促进了移植细胞的保留。超声心动图和心脏磁共振成像(CMR)显示,在治疗 12 个月后,胶原/hUMSC 组的左心室射血分数(LVEF)明显高于 hUMSC 组和安慰剂组,梗死面积百分比也明显低于 hUMSC 组和安慰剂组。胶原/细胞组梗死边缘区的 vWf、α-sma 和 cTnT 阳性细胞密度也较高,免疫组织化学分析表明,心肌梗死后血管生成和心肌细胞存活更好。因此,可注射胶原支架在大型动物心肌模型中是安全有效的,有利于构建有利于临床 MI 中应用干细胞的有利微环境。

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