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心肌梗死后心肌细胞移植改变心脏的免疫反应。

Cardiomyocyte Transplantation after Myocardial Infarction Alters the Immune Response in the Heart.

机构信息

Department of Cardiac Surgery, Rostock University Medical Centre, 18057 Rostock, Germany.

Department of Life, Light and Matter, University of Rostock, 18059 Rostock, Germany.

出版信息

Cells. 2020 Aug 3;9(8):1825. doi: 10.3390/cells9081825.

DOI:10.3390/cells9081825
PMID:32756334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7465503/
Abstract

We investigated the influence of syngeneic cardiomyocyte transplantation after myocardial infarction (MI) on the immune response and cardiac function. Methods and Results: We show for the first time that the immune response is altered as a result of syngeneic neonatal cardiomyocyte transplantation after MI leading to improved cardiac pump function as observed by magnetic resonance imaging in C57BL/6J mice. Interestingly, there was no improvement in the capillary density as well as infarct area as observed by CD31 and Sirius Red staining, respectively. Flow cytometric analysis revealed a significantly different response of monocyte-derived macrophages and regulatory T cells after cell transplantation. Interestingly, the inhibition of monocyte infiltration accompanied by cardiomyocyte transplantation diminished the positive effect of cell transplantation alone. The number of CD68+ macrophages in the remote area of the heart observed after four weeks was also different between the groups. Transcriptome analysis showed several changes in the gene expression involving circadian regulation, mitochondrial metabolism and immune responses after cardiomyocyte transplantation. Conclusion: Our work shows that cardiomyocyte transplantation alters the immune response after myocardial infarction with the recruited monocytes playing a role in the beneficial effect of cell transplantation. It also paves the way for further optimization of the efficacy of cardiomyocyte transplantation and their successful translation in the clinic.

摘要

我们研究了心肌梗死后同种异体心肌细胞移植对免疫反应和心功能的影响。方法和结果：我们首次表明，由于同种异体新生心肌细胞移植后导致免疫反应发生改变，从而导致 C57BL/6J 小鼠的磁共振成像观察到心泵功能改善。有趣的是，通过 CD31 和 Sirius Red 染色分别观察到毛细血管密度和梗死面积没有改善。流式细胞术分析显示，细胞移植后单核细胞衍生的巨噬细胞和调节性 T 细胞的反应明显不同。有趣的是，抑制单核细胞浸润伴随着心肌细胞移植，减弱了单独细胞移植的积极作用。移植后 4 周时，心脏远隔区观察到的 CD68+巨噬细胞数量在各组之间也不同。转录组分析显示，心肌细胞移植后涉及昼夜节律调节、线粒体代谢和免疫反应的几个基因表达发生变化。结论：我们的工作表明，心肌细胞移植改变了心肌梗死后的免疫反应，募集的单核细胞在细胞移植的有益作用中发挥作用。它还为进一步优化心肌细胞移植的疗效及其在临床上的成功转化铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/138fff3e1de6/cells-09-01825-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/b3eb4b0307c9/cells-09-01825-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/8230c348047d/cells-09-01825-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/c8ac697200f8/cells-09-01825-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/005aae20aebd/cells-09-01825-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/4d800bb812d3/cells-09-01825-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/138fff3e1de6/cells-09-01825-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/b3eb4b0307c9/cells-09-01825-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/8230c348047d/cells-09-01825-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/c8ac697200f8/cells-09-01825-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/005aae20aebd/cells-09-01825-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/4d800bb812d3/cells-09-01825-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/7465503/138fff3e1de6/cells-09-01825-g006.jpg

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