小柯机器人

美国辛辛那提大学Jeffery D. Molkentin研究团队在研究中取得进展。他们发现急性免疫反应是心脏干细胞治疗疗效的基础。该项研究成果2019年11月27日在线发表在《自然》上。

研究人员检查了缺血/再灌注（I/R）损伤后小鼠细胞治疗的机制基础，虽然心脏功能得到了增强，但它与新的心肌细胞的产生无关。细胞疗法通过急性无菌免疫反应改善了心脏功能，其特征在于CCR2和CX3CR1双阳性巨噬细胞的时间和区域诱导。心脏内注射2种不同类型的成年干细胞，冻融/杀死细胞或先天免疫应答的化学诱导剂类似地诱导了区域CCR2和CX3CR1双阳性巨噬细胞积累，并为I/R损伤的心脏提供了功能恢复。这种选择性的巨噬细胞反应改变了心脏成纤维细胞的活性，减少了边界区细胞外基质的含量，并增强了受伤部位的机械性能。因此，心脏细胞治疗的功能优势是由于基于急性炎症的伤口愈合反应，可以使心脏梗塞区域的机械特性恢复活力。

据介绍，直到今天，使用成体干细胞再生受损心脏组织的临床试验仍在继续，尽管仍存在有效性问题，并且对潜在的生物学效应缺乏机械理解。这些细胞疗法试验的基本原理来自动物研究，这些研究表明，在心脏缺血性损伤模型中，心脏功能有适度但可重现的改善。

附：英文原文

Title: An acute immune response underlies the benefit of cardiac stem-cell therapy

Author: Ronald J. Vagnozzi, Marjorie Maillet, Michelle A. Sargent, Hadi Khalil, Anne Katrine Johansen, Jennifer A. Schwanekamp, Allen J. York, Vincent Huang, Matthias Nahrendorf, Sakthivel Sadayappan, Jeffery D. Molkentin

Issue&Volume: 2019-11-27

Abstract: Clinical trials using adult stem cells to regenerate damaged heart tissue continue to this day1,2 despite ongoing questions of efficacy and a lack of mechanistic understanding of the underlying biologic effect3. The rationale for these cell therapy trials is derived from animal studies that show a modest but reproducible improvement in cardiac function in models of cardiac ischemic injury4,5. Here we examined the mechanistic basis for cell therapy in mice after ischemia/reperfusion (I/R) injury, and while heart function was enhanced, it was not associated with new cardiomyocyte production. Cell therapy improved heart function through an acute sterile immune response characterized by the temporal and regional induction of CCR2+ and CX3CR1+ macrophages. Intra-cardiac injection of 2 distinct types of adult stem cells, freeze/thaw-killed cells or a chemical inducer of the innate immune response similarly induced regional CCR2+ and CX3CR1+ macrophage accumulation and provided functional rejuvenation to the I/R-injured heart. This selective macrophage response altered cardiac fibroblast activity, reduced border zone extracellular matrix (ECM) content, and enhanced the mechanical properties of the injured area. The functional benefit of cardiac cell therapy is thus due to an acute inflammatory-based wound healing response that rejuvenates the mechanical properties of the infarcted area of the heart.

DOI: 10.1038/s41586-019-1802-2

Source:https://www.nature.com/articles/s41586-019-1802-2

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html