Targeted delivery of bone marrow mononuclear cells by ultrasound destruction of microbubbles induces both angiogenesis and arteriogenesis response
Targeted delivery of bone marrow mononuclear cells by ultrasound destruction of microbubbles induces both angiogenesis and arteriogenesis response
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DOI：
10.1161/01.atv.0000179768.06206.cb
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发表时间：
2005-10-01
影响因子：
8.7
通讯作者：
Matsubara, H
中科院分区：
文献类型：
--
作者：
Imada, T;Tatsumi, T;Matsubara, H
目的：超声(US)介导的造影剂微泡破坏导致毛细血管破裂，从而刺激动脉生成，而骨髓单个核细胞(BM-MNC)肌肉内植入(Im)则诱导血管生成。因此，我们研究了超声靶向微泡破坏联合BM-MNCs移植是否可以通过刺激血管生成和动脉生成来促进血流恢复。方法和结果：将超声介导的磷脂包裹的微泡破坏应用于缺血的后肢肌肉，然后输注BM-MNCs。输注Bubble+US+BM-MNC后血流恢复较Bubble+US组(25%)显著增加(34%，P<；0.05)。Bubble+US+BM-MNC-i.v组的毛细血管/肌纤维比(260%，P<0.01)明显高于Bubble+US组(172%)。平滑肌α-肌动蛋白阳性小动脉也增加，血管造影术显示侧支血管形成增加(动脉生成)。由Bubble+US激活的血小板源性促炎因子诱导黏附分子(P-选择素和ICAM-1)的表达，导致移植的BM-MNC与内皮细胞黏附。流式细胞仪检测证实，在层流状态下，BM-MNCs与内皮细胞的黏附是由血小板衍生因子引起的。结论--本研究证实了超声破坏微泡后靶向输送BM-MNCs可增强局部血管生成和动脉生成反应，其中由Bubble+US激活的血小板衍生促炎因子的释放在移植的BM-MNCs黏附于内皮层中起关键作用。
Objective - Ultrasound (US)-mediated destruction of contrast microbubbles causes capillary rupturing that stimulates arteriogenesis, whereas intramuscular implantation (im) of bone marrow mononuclear cells (BM-MNCs) induces angiogenesis. We therefore studied whether US-targeted microbubble destruction combined with transplantation of BM-MNCs can enhance blood flow restoration by stimulating both angiogenesis and arteriogenesis.Methods and Results - US-mediated destruction of phospholipid-coated microbubbles was applied onto ischemic hindlimb muscle and subsequently BM-MNCs were transfused. A significant enhancement in blood flow recovery after Bubble + US + BM-MNC infusion (34% increase, P < 0.05) was observed compared with Bubble + US (25%). The ratio of capillary/muscle fiber increased by Bubble + US + BM-MNC-i.v (260%, P < 0.01) than that in the Bubble + US group (172%), into which BM-MNCs were incorporated ( angiogenesis). Smooth muscle alpha-actin - positive arterioles were also increased, and angiography showed augmented collateral vessel formation ( arteriogenesis). Platelet-derived proinflammatory factors activated by Bubble + US induces the expression of adhesion molecules (P-selectin and ICAM-1), leading to the attachment of transplanted BM-MNCs on the endothelium. Flow assay confirmed that the platelet-derived factors cause the adhesion of BM-MNCs onto endothelium under laminar flow.Conclusions - This study demonstrates that the targeted delivery of BM-MNCs by US destruction of microbubbles enhances regional angiogenesis and arteriogenesis response, in which the release of platelet-derived proinflammatory factors activated by Bubble + US play a key role in the attachment of transplanted BM-MNCs onto the endothelial layer.