祖細(xì)胞（progenitor cell，PC）或者干細(xì)胞從骨髓（bone marrow，BM）中動(dòng)員到缺血性心臟受損部位是一種生理性的修復(fù)反應(yīng)。此前，人們已經(jīng)使用骨髓祖細(xì)胞或干細(xì)胞進(jìn)行了大量的細(xì)胞治療臨床試驗(yàn)，證明骨髓祖細(xì)胞或干細(xì)胞對(duì)缺血性心肌損傷的有益修復(fù)作用。但是，人們對(duì)骨髓祖細(xì)胞或干細(xì)胞的轉(zhuǎn)運(yùn)和招募機(jī)制依然不是十分清楚。

有研究發(fā)現(xiàn)，心肌來(lái)源的microRNAs（miRNA）在急性心肌梗死后會(huì)釋放到體循環(huán)中，研究人員猜測(cè)這些miRNA可能影響遠(yuǎn)端其他器官的功能。近日，來(lái)自華中科技大學(xué)同濟(jì)醫(yī)學(xué)院附屬協(xié)和醫(yī)院和美國(guó)阿拉巴馬大學(xué)伯明翰分校的研究人員在Nature communications雜志發(fā)表文章，報(bào)道了心肌梗死后其梗死部位會(huì)分泌外泌體miRNA到外周血中，并轉(zhuǎn)移至骨髓單核細(xì)胞中促進(jìn)祖細(xì)胞的動(dòng)員，促進(jìn)心血管修復(fù)。該研究探索了循環(huán)中在心肌表達(dá)豐度很高的miRNA（myo-miRNA）和外泌體在急性心肌梗死（acute myocardial infarction，AMI）模型小鼠中的作用。結(jié)果顯示，循環(huán)myo-miRNA在外泌體中攜帶并介導(dǎo)缺血心臟組織和骨髓之間的功能性聯(lián)系。在心臟發(fā)生損傷后，梗死部位的myo-miRNA迅速釋放到外周血里，這些miRNA主要被包裹在外泌體中。在小鼠中，AMI伴隨著循環(huán)myo-miRNA水平的增加，其中miR-1208和miR-499主要被包裹在循環(huán)外泌體中，而miR-133在非外泌體組分中。此外，研究發(fā)現(xiàn)myo-miRNA選擇性地被外周器官所攝取，優(yōu)先進(jìn)入骨髓中。同時(shí)，外泌體介導(dǎo)的myo-miRNA向骨髓單核細(xì)胞（mononuclear cells，MNC）轉(zhuǎn)移，其包裹的myo-miRNA會(huì)下調(diào)CXCR4表達(dá)。當(dāng)研究人員將從AMI小鼠分離的外泌體注射到野生型小鼠中，發(fā)現(xiàn)野生型小鼠骨髓單核細(xì)胞中的CXCR4表達(dá)下調(diào)、循環(huán)祖細(xì)胞的數(shù)量增加。

根據(jù)這一系列研究結(jié)果，研究人員提出循環(huán)外泌體中攜帶的myo-miRNA會(huì)引起心臟缺血性損傷后的全身反應(yīng)，具有缺損心臟組織修復(fù)潛力。

推薦閱讀原文：

Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilize bone marrow progenitor cells.

Myocardial microRNAs (myo-miRs) are released into the circulation after acute myocardial infarction (AMI). How they impact remote organs is however largely unknown. Here we show that circulating myo-miRs are carried in exosomes and mediate functional crosstalk between the ischemic heart and the bone marrow (BM). In mice, we find that AMI is accompanied by an increase in circulating levels of myo-miRs, with miR-1, 208, and 499 predominantly in circulating exosomes and miR-133 in the non-exosomal component. Myo-miRs are imported selectively to peripheral organs and preferentially to the BM. Exosomes mediate the transfer of myo-miRs to BM mononuclear cells (MNCs), where myo-miRs downregulate CXCR4 expression. Injection of exosomes isolated from AMI mice into wild-type mice downregulates CXCR4 expression in BM-MNCs and increases the number of circulating progenitor cells. Thus, we propose that myo-miRs carried in circulating exosomes allow a systemic response to cardiac injury that may be leveraged for cardiac repair.