Circulation：干细胞因子微粒或可预防婴儿肺部疾病

来自波士顿儿童医院的研究者通过研究发现，含有蛋白质以及外核体（核酸）的微观粒子可以保护早产儿脆弱的肺部免于严重的肺疾病以及由于炎症所引发的慢性肺损伤。这项研究刊登于国际杂志Circulation上，或可解释，移植间质干细胞（MSCs）可以降低肺部损伤以及阻止小鼠模型的肺部炎症。

早产儿通常会因为肺部功能不全而引发缺氧和呼吸障碍，其肺部对于验证极其敏感，炎症或可引发肺部生长异常以及慢性肺疾病。该项研究中，研究者发现，通过注射从MSCs中纯化的外核体可以降低肺部高血压动物模型的肺部炎症以及组织肺部高血压的复发。相反，无任何外核体作用的动物模型并不会对其炎症有任何影响。这就表明，MSCs产生的外核体存在一种保护效应。

研究者Kourembanas说，我们将深入研究为何MSC的外核体可以产生抗炎以及保护效应，但是我们知道外核体包含有microRNA和其它核酸，其同样可以在接受者的肺部中诱导特殊的microRNA的表达。microRNA是一种小片段的RNA分子，其可以调节基因的表达活性。

研究者认为，外核体的研究将为开发基于干细胞的新型疗法提供帮助，未来研究中，MSC产生的外核体将会作为一种直接的疗法用于治疗处于慢性肺部疾病以及肺部高血压的婴儿。

外核体可以以不同的来源从MSCs细胞中分离，包括从脐带中分离。不像供体细胞，外核体并不具有免疫原性，其可以被收集、积累然后就像药物一样，并不具有任何注射风险以及肿瘤生成风险。

相关研究由国立心脏、肺部和血液研究所提供资助。

与干细胞相关的拓展阅读：

• Oncogenesis：揭示维生素A降低前列腺癌干细胞侵袭性机制
• JOT：骨髓干细胞移植对滥用酒精大鼠模型骨折愈合的影响
• Clin Cancer Res. ：在HER2阴性乳腺癌中鉴定出HER2阳性干细胞
• Acta Biomater：新型干细胞装载运输技术可帮助眼睛受损者重获光明
• PLoS ONE：成功将成人胰腺干细胞转化为胰岛素产生细胞
• JAMA：干细胞修复心脏受损组织
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Exosomes Mediate the Cytoprotective Action of Mesenchymal Stromal Cells on Hypoxia-Induced Pulmonary Hypertension

Background—Hypoxia induces an inflammatory response in the lung manifested by alternative activation of macrophages with elevation of pro-inflammatory mediators that are critical for the later development of hypoxic pulmonary hypertension (HPH). Mesenchymal stromal cell (MSC) transplantation inhibits lung inflammation, vascular remodeling and right heart failure, and reverses HPH in experimental models of disease. In this study, we aimed to investigate the paracrine mechanisms by which MSCs are protective in HPH. Methods and Results—We fractionated mouse MSC-conditioned media to identify the biologically-active component affecting in vivo hypoxic signaling and determined that exosomes, secreted membrane microvesicles, suppressed the hypoxic pulmonary influx of macrophages and the induction of pro-inflammatory and pro-proliferative mediators, including monocyte chemoattractant protein-1 and hypoxia-inducible mitogenic factor, in the murine model of HPH. Intravenous delivery of MSC-derived exosomes (MEX) inhibited vascular remodeling and HPH, whereas MEX-depleted media or fibroblast-derived exosomes had no effect. MEX suppressed the hypoxic activation of signal transducer and activator of transcription 3 (STAT3) and the upregulation of the miR-17 superfamily of microRNA clusters, whereas it increased lung levels of miR-204, a key microRNA whose expression is decreased in human PH. MEX produced by human umbilical cord MSCs inhibited STAT3 signaling in isolated human pulmonary artery endothelial cells demonstrating a direct effect of MEX on hypoxic vascular cells. Conclusions—This study indicates that MEX exert a pleiotropic protective effect on the lung and inhibit PH through suppression of hyperproliferative pathways, including STAT-3 mediated signaling induced by hypoxia.