Stem Cell Therapy for Arterial Restenosis: Potential Parameters Contributing to the Success of Bone Marrow-Derived Mesenchymal Stromal Cells
Stem Cell Therapy for Arterial Restenosis: Potential Parameters Contributing to the Success of Bone Marrow-Derived Mesenchymal Stromal Cells
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DOI：
10.1007/s10557-011-6359-8
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发表时间：
2012-02-01
影响因子：
3.4
通讯作者：
Cipollaro, Marilena
中科院分区：
文献类型：
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作者：
Forte, Amalia;Rinaldi, Barbara;Cipollaro, Marilena
目的再狭窄是血管重建术患者发生的一种复杂且异质性的病理生理现象。先前的研究证实了注射同种异体间充质间质细胞（MSCs）在大鼠动脉切开术所致颈动脉狭窄实验模型中的抗再狭窄特性。在这项研究中，我们描述了颈动脉切开术大鼠接受MSC治疗后的一些影响，可能是其抗再狭窄作用的原因。方法从大鼠骨髓中分离骨髓间充质干细胞，进行体外扩增和鉴定。随后，我们评估了颈动脉切除后3和7天通过尾静脉给药MSC对大鼠血清和受损颈动脉的影响，重点关注DNA氧化损伤（8-oxo-dG检测）、细胞增殖指数（BrdU掺入试验）、凋亡指数（TUNEL试验）、炎症和增殖相关基因的表达（RT-PCR）、生长因子和炎症相关细胞因子的释放（抗体序列和ELISA）。结果骨髓间充质干细胞可诱导动脉切开后大鼠颈动脉内细胞增殖增强，血清中VEGF水平升高，损伤颈动脉内VEGF mRNA表达升高。血清分析还显示，msc处理大鼠的促炎细胞因子CXCL1、CXCL5、l -选择素、ICAM-1和LIX以及TIMP1和sdf -1 α水平降低。损伤颈动脉中TLR2和TLR4的表达降低证实了MSC的免疫调节作用。结论颈动脉切开大鼠注射MSCs具有免疫调节的旁分泌作用，并伴有VEGF的释放，可能促进了损伤血管壁的加速修复。
Purpose Restenosis is a complex and heterogeneous pathophysiological phenomenon occurring in patients submitted to revascularization procedures. Previous studies proved the antirestenotic properties of injected allogenic mesenchymal stromal cells (MSCs) in an experimental model of rat carotid (re) stenosis induced through arteriotomy. In this study we describe some of the effects subsequent to MSC treatment of rats submitted to carotid arteriotomy and possibly responsible for their antirestenotic effect.Methods Rat MSCs were isolated from bone marrow, expanded in vitro and characterized. Subsequently, we evaluated the effects of MSC administration via tail vein at 3 and 7 days after carotid arteriotomy both in rat serum and in injured carotids, focusing on DNA oxidative damage (8-oxo-dG detection), cell proliferation index (BrdU incorporation assay), apoptotic index (TUNEL assay), the expression of inflammation-and proliferation-related genes (RT-PCR), the release of growth factors and of inflammation-related cytokines (antibody arrays and ELISA).Results MSC administration induced a greater cell proliferation in carotids after arteriotomy, together with an increased level of VEGF in the serum and with the higher expression of VEGF mRNA in injured carotids. Serum analysis also revealed a decreased level of the pro-inflammatory cytokines CXCL1, CXCL5, L-Selectin, ICAM-1 and LIX, and of TIMP1 and SDF-1alpha in MSC-treated rats. The MSC immunomodulatory activity was confirmed by the decreased expression of TLR2 and TLR4 in injured carotids.Conclusions MSCs play an immunomodulatory paracrine role when injected in rats submitted to carotid arteriotomy, accompanied by the release of VEGF, possibly contributing to the accelerated repair of the injured vascular wall.