Myocardial infarction stabilization by cell-based expression of controlled Vascular Endothelial Growth Factor levels.
Myocardial infarction stabilization by cell-based expression of controlled Vascular Endothelial Growth Factor levels.
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DOI：
10.1111/jcmm.13511
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发表时间：
2018-05
影响因子：
5.3
通讯作者：
Banfi A
中科院分区：
文献类型：
--
作者：
Melly L;Cerino G;Frobert A;Cook S;Giraud MN;Carrel T;Tevaearai Stahel HT;Eckstein F;Rondelet B;Marsano A;Banfi A
血管内皮生长因子（VEGF）可以诱导正常或异常的血管生成，这取决于每个细胞周围微环境中分泌的量。为了可能的临床转化，我们开发了一种基于荧光激活细胞分选（FACS）的技术，以快速纯化来自异质原代群体的均匀表达所需特异性VEGF水平的转导祖细胞。在这里，我们试图通过控制VEGF水平的细胞表达来诱导缺血心肌中安全和功能性的血管生成。用逆转录病毒载体转导人脂肪基质细胞（ASC），并进行FACS纯化，以产生两个群体，产生相似的总VEGF剂量，但具有不同的分布：一个群体具有均匀产生特定VEGF水平的细胞（SPEC），另一个群体具有不均匀产生广泛VEGF水平的细胞（ALL），但平均值与SPEC群体相似。共70只裸鼠通过冠状动脉结扎进行心肌梗死，2周后在梗死边缘注射VEGF表达细胞或对照细胞或生理盐水。四周后，除SPEC细胞外，所有治疗组的心室射血分数均显著恶化。此外，只有SPEC细胞显着增加了均匀正常和成熟微血管网络的密度。这伴随着积极的重塑作用，梗死区的纤维化显著减少。我们的结论是，通过FACS纯化的转导ASC控制均匀的VEGF递送是一种很有前途的策略，可以在心肌缺血中实现安全和功能性的血管生成。
Vascular Endothelial Growth Factor (VEGF) can induce normal or aberrant angiogenesis depending on the amount secreted in the microenvironment around each cell. Towards a possible clinical translation, we developed a Fluorescence Activated Cell Sorting (FACS)‐based technique to rapidly purify transduced progenitors that homogeneously express a desired specific VEGF level from heterogeneous primary populations. Here, we sought to induce safe and functional angiogenesis in ischaemic myocardium by cell‐based expression of controlled VEGF levels. Human adipose stromal cells (ASC) were transduced with retroviral vectors and FACS purified to generate two populations producing similar total VEGF doses, but with different distributions: one with cells homogeneously producing a specific VEGF level (SPEC), and one with cells heterogeneously producing widespread VEGF levels (ALL), but with an average similar to that of the SPEC population. A total of 70 nude rats underwent myocardial infarction by coronary artery ligation and 2 weeks later VEGF‐expressing or control cells, or saline were injected at the infarction border. Four weeks later, ventricular ejection fraction was significantly worsened with all treatments except for SPEC cells. Further, only SPEC cells significantly increased the density of homogeneously normal and mature microvascular networks. This was accompanied by a positive remodelling effect, with significantly reduced fibrosis in the infarcted area. We conclude that controlled homogeneous VEGF delivery by FACS‐purified transduced ASC is a promising strategy to achieve safe and functional angiogenesis in myocardial ischaemia.
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影响因子：
20.1
作者：
Kanelidis AJ;Premer C;Lopez J;Balkan W;Hare JM
通讯作者：
Hare JM
影响因子：
82.9
作者：
Kocher, AA;Schuster, MD;Itescu, S
通讯作者：
Itescu, S
影响因子：
17.1
作者：
De Ravin SS;Wu X;Moir S;Anaya-O'Brien S;Kwatemaa N;Littel P;Theobald N;Choi U;Su L;Marquesen M;Hilligoss D;Lee J;Buckner CM;Zarember KA;O'Connor G;McVicar D;Kuhns D;Throm RE;Zhou S;Notarangelo LD;Hanson IC;Cowan MJ;Kang E;Hadigan C;Meagher M;Gray JT;Sorrentino BP;Malech HL;Kardava L
通讯作者：
Kardava L
影响因子：
5.4
作者：
Gogiraju R;Xu X;Bochenek ML;Steinbrecher JH;Lehnart SE;Wenzel P;Kessel M;Zeisberg EM;Dobbelstein M;Schäfer K
通讯作者：
Schäfer K
影响因子：
5.4
作者：
Boden J;Lassance-Soares RM;Wang H;Wei Y;Spiga MG;Adi J;Layman H;Yu H;Vazquez-Padron RI;Andreopoulos F;Webster KA
通讯作者：
Webster KA