Cardiac resident nestin plus cells participate in reparative vascularisation
Cardiac resident nestin plus cells participate in reparative vascularisation
复制标题
DOI：
10.1002/jcp.24345
复制
发表时间：
2013-09-01
影响因子：
5.6
通讯作者：
Calderone, Angelino
中科院分区：
文献类型：
--
作者：
El-Helou, Vivianne;Chabot, Andreanne;Calderone, Angelino
啮齿动物心脏含有一群源自胚胎神经嵴的巢蛋白（+）细胞，并在心肌梗塞（MI）后迁移到疤痕处。本研究检验了巢蛋白基因内含子 2 驱动表达以及巢蛋白 (+) 细胞亚群参与修复性血管形成的假设。巢蛋白基因第二个内含子的绿色荧光蛋白（GFP）的定向表达鉴定出嵌入正常转基因小鼠心脏的心室肌细胞中的GFP/巢蛋白（+）细胞。缺血性损伤导致 GFP(+) 细胞迁移至疤痕，并在新形成的血管的 CD31/nestin(+) 内皮细胞中检测到一个亚群。对修复性血管形成的直接贡献为检验以下假设提供了动力：增加梗塞心脏中巢蛋白（+）细胞的数量将改善疤痕愈合。从 E18 SpragueDawley 大鼠中分离的皮肤源性细胞生长为球体，表达巢蛋白、sox2、神经嵴相关转录基因和一组肽生长因子。移植到 MI 后 3 天的大鼠非梗塞左心室的皮肤源性细胞迁移到梗塞周围/梗塞区域，并保持移植状态 21 天。在移植的梗塞大鼠心脏中观察到梗塞明显缩小、小口径血管数量增加以及心室功能改善。因此，巢蛋白基因的第二个内含子驱动小鼠心脏中的表达，并且GFP/巢蛋白(+)细胞亚群直接参与修复性血管形成。通过移植皮肤来源的细胞来增加巢蛋白（+）细胞的数量是限制心脏缺血性损伤的潜在方法。 J.细胞。生理学。 228：18441853，2013 年。(c) 2013 年 Wiley 期刊公司。
The rodent heart contains a population of nestin(+) cells derived from the embryonic neural crest and migrate to the scar after myocardial infarction (MI). The present study tested the hypothesis that intron 2 of the nestin gene drives expression and a subpopulation of nestin(+) cells participate in reparative vascularisation. The directed expression of the green fluorescent protein (GFP) by the second intron of the nestin gene identified GFP/nestin(+) cells intercalated among ventricular myocytes in the heart of normal transgenic mice. Ischemic injury led to the migration of GFP(+) cells to the scar and a subpopulation was detected in CD31/nestin(+) endothelial cells of newly formed blood vessels. The direct contribution to reparative vascularisation provided the impetus to test the hypothesis that increasing the population of nestin(+) cells in the infarcted heart will improve scar healing. Skin-derived cells isolated from E18 SpragueDawley rats grew as spheres, expressed nestin, sox2, neural crest-related transcriptional genes and a panel of peptide growth factors. Skin-derived cells transplanted in the non-infarcted left ventricle of 3-day post-MI rats migrated to the peri-infarct/infarct region and remained engrafted for 21 days. A significantly smaller infarct, increased number of small calibre blood vessels and improved ventricular function were observed in engrafted infarcted rat hearts. Thus, the second intron of the nestin gene drives expression in the mouse heart and a subpopulation of GFP/nestin(+) cells directly participate in reparative vascularisation. Increasing the population of nestin(+) cells via the transplantation of skin-derived cells represents a potential approach to limit ischemic damage to the heart. J. Cell. Physiol. 228: 18441853, 2013. (c) 2013 Wiley Periodicals, Inc.