P593Human vascular pericytes and cardiac progenitor cells combined transplantation for heart repair
P593Human vascular pericytes and cardiac progenitor cells combined transplantation for heart repair
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P593人血管周细胞与心脏祖细胞联合移植用于心脏修复
DOI：
10.1093/cvr/cvu098.23
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发表时间：
2014
影响因子：
10.8
通讯作者：
Avolio E
中科院分区：
文献类型：
--
作者：
Avolio E
目的：在心肌梗死（MI）小鼠模型中比较隐静脉来源的周细胞（SVP）与c-Kit-pos心脏祖细胞（CPC）的再生潜力，并研究细胞的同时移植是否会产生附加改善。方法：从移植心脏废弃的心房标本中分离CPCs;从CABG患者的静脉残余物中免疫分选SVP。根据细胞的表面表型和向3种心脏谱系的分化能力，在体外比较细胞。在MI后14和42天，比较注射媒介物（n= 6）、CPC（n= 6）、SVP（n= 6）或CPC + SVP（n= 6）（每种类型的300，000个细胞/心脏）的SCID-米色小鼠梗塞心脏的功能恢复。在体外研究了SVP与CPC、分泌体和旁分泌效应之间的相互作用。结果如下：SVP和CPC均表达间充质标记（CD 44/CD 90/CD 105），对内皮和造血抗原呈阴性，并表达干性标记Sox 2。此外，SVP表达周细胞标志物NG 2和PDGFRb。两种细胞类型分泌相似的旁分泌因子（HGF、VEGF、FGF、SCF），并补充有关于SVP的Ang-1和-2。重要的是，细胞共培养48小时增加了SDF-1的分泌。CPC在内皮细胞和血管肌细胞中分化，而两种细胞类型在暴露于诱导培养基21天时获得心肌细胞标记物。与载体相比，细胞移植在MI后14天和42天同样改善了体积、收缩性和压力指数，联合治疗没有累加效应。同样，两种细胞类型都刺激了心肌愈合，保护心肌细胞免于凋亡并增加内源性CPC的密度;联合治疗没有进一步改善。当暴露于SVP条件培养基时，与普通培养基相比，CPC倾向于增加迁移。RNA酶或酪氨酸和丝氨酸/苏氨酸激酶受体抑制剂或阻断抗体混合物（HGF、FGF、VEGF、SCF和Tie 2）不会消除或减弱这种反应。蛋白酶K预处理能够消除响应，不同于加热变性。通过分子量分级SVP条件培养基显示分泌的化学引诱因子> 10 kDa。结论：SVP在治疗上与CPC等效。更容易获得的来源使SVP成为心肌修复细胞治疗中CPC的最佳替代品。此外，对损伤部位的CPC的吸引作用有利于内源性心脏再生。[出版商摘要]《心血管研究》的版权归牛津大学出版社/美国所有，未经版权保持器明确书面许可，不得将其内容复制或通过电子邮件发送到多个网站或发布到列表服务器。但是，用户可以打印、下载或通过电子邮件发送文章供个人使用。这篇摘要可以删节。对副本的准确性不作任何保证。用户应参考材料的原始出版版本以获取完整摘要。版权适用于所有摘要。
Purpose: to compare the regenerative potential of Saphenous Vein-derived Pericytes (SVPs) with that of c-Kit-pos Cardiac Progenitor Cells (CPCs) in a mouse model of myocardial infarction (MI), and to investigate if the simultaneus transplantation of the cells produces additive improvements. Methods: CPCs were isolated from discarded atrial specimens of transplanted hearts; SVPs were immune-sorted from vein leftovers of CABG patients. Cells were compared in vitro according to their surface-phenotype and differentiation ability toward the 3 cardiac lineages. The functional recovery of SCID-Beige mice infarcted hearts injected with Vehicle (n= 6), CPCs (n= 6), SVPs (n= 6) or CPCs+ SVPs (n= 6)(300,000 cells of each type/heart) was compared, both 14 and 42 days post-MI. Interaction between SVPs and CPCs, secretomes, and paracrine effects were investigated in vitro. Results: both SVPs and CPCs express mesenchymal markers (CD44/CD90/CD105), are negative for endothelial and hematopoietic antigens and express the stemness markers Sox2. In addition, SVPs express the pericyte markers NG2 and PDGFRb. Both cell types secrete similar paracrine factors (HGF, VEGF, FGF, SCF), supplemented by Ang-1 and-2 regarding SVPs. Importantly, co-culture of cells for 48h increased the secretion of SDF-1. CPCs differentiate in endothelial and vascular muscle cells, while both cell types acquire cardiomyocyte markers when exposed for 21 days to an inductive culture medium. Cell transplantation similarly improved volume, contractility and pressure indexes at 14 and 42 days post-MI compared to vehicle, with no additive effect by combined therapy. Similarly, myocardial healing was stimulated by both the cell types, protecting cardiomyocytes from apoptosis and increasing the density of endogenous CPCs; the combined therapy did not add further improvements. When exposed to SVP conditioned media, CPCs tend to increase migration compared to plain media. This response is not abrogated or diminished by RNAase or tyrosine and serine/threonine kinase receptor inhibitors, or a blocking antibodies cocktail (HGF, FGF, VEGF, SCF, and Tie2). Proteinase K pretreatment was able to abrogate the response, differently from the heating denaturation. Fractioning SVP conditioned medium by molecular weight showed that secreted chemoattractant factor is > 10 kDa. Conclusions: SVPs are therapeutically equipotent to CPCs. The more accessible source makes SVPs an optimal alternative to CPCs in cell therapy for myocardial repair. Moreover, the attractant effect on CPCs in the site of injury favours the endogenous cardiac regeneration.[ABSTRACT FROM PUBLISHER]Copyright of Cardiovascular Research is the property of Oxford University Press/USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. Copyright applies to all Abstracts.