Bone marrow-derived mesenchymal stem cells inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia after arterial injury in rats.
Bone marrow-derived mesenchymal stem cells inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia after arterial injury in rats.
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DOI：
10.1016/j.bbrep.2018.10.001
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发表时间：
2018-12
影响因子：
2.7
通讯作者：
Suzuki H
中科院分区：
文献类型：
--
作者：
Iso Y;Usui S;Toyoda M;Spees JL;Umezawa A;Suzuki H
我们研究了基于间充质干细胞（MSC）的治疗是否可以抑制大鼠颈动脉损伤模型中的新生内膜增生，并探讨了MSC治疗对血管重塑/修复的积极作用的潜在机制。Sprague-Dawley大鼠右颈动脉球囊损伤。2天后，我们将转基因gfp大鼠骨髓培养的MSCs（0.8 × 106个细胞，n = 10）或对照（n = 10）注射到损伤动脉的外膜部位。作为额外的对照，一些大鼠通过全身输注更高剂量的MSCs（3 × 106个细胞，尾静脉；n = 4）。在治疗后14天，局部血管给予MSC可显著防止新内膜增生（内膜/中膜比率），并降低动脉壁中Ki67 +增殖细胞的百分比，尽管没有证据表明长期植入MSC。值得注意的是，全身骨髓间充质干细胞输注没有改变新生内膜的形成。通过免疫组化，与对照组的新生内膜细胞相比，msc处理的动脉细胞表达的胚胎肌球蛋白重链和炎症细胞标志物RM-4水平降低。在血小板衍生生长因子（PDGF-BB）存在的情况下，MSCs的条件培养基增加了p27蛋白水平，并显著减弱了VSMC的增殖。此外，msc条件培养基抑制pdgf - bb处理的VSMCs中炎症细胞因子和RM-4的表达。因此，血管周围给药MSCs可能通过调节VSMC炎症表型的旁分泌作用改善血管损伤后的再狭窄。局部骨髓间充质干细胞治疗可抑制大鼠动脉损伤后新内膜的形成。局部骨髓间充质干细胞治疗可调节动脉损伤后VSMC表型。msmc分泌因子抑制VSMC增殖，改变表型。
We investigated whether mesenchymal stem cell (MSC)-based treatment could inhibit neointimal hyperplasia in a rat model of carotid arterial injury and explored potential mechanisms underlying the positive effects of MSC therapy on vascular remodeling/repair. Sprague-Dawley rats underwent balloon injury to their right carotid arteries. After 2 days, we administered cultured MSCs from bone marrow of GFP-transgenic rats (0.8 × 106 cells, n = 10) or vehicle (controls, n = 10) to adventitial sites of the injured arteries. As an additional control, some rats received a higher dose of MSCs by systemic infusion (3 × 106 cells, tail vein; n = 4). Local vascular MSC administration significantly prevented neointimal hyperplasia (intima/media ratio) and reduced the percentage of Ki67 + proliferating cells in arterial walls by 14 days after treatment, despite little evidence of long-term MSC engraftment. Notably, systemic MSC infusion did not alter neointimal formation. By immunohistochemistry, compared with neointimal cells of controls, cells in MSC-treated arteries expressed reduced levels of embryonic myosin heavy chain and RM-4, an inflammatory cell marker. In the presence of platelet-derived growth factor (PDGF-BB), conditioned medium from MSCs increased p27 protein levels and significantly attenuated VSMC proliferation in culture. Furthermore, MSC-conditioned medium suppressed the expression of inflammatory cytokines and RM-4 in PDGF-BB-treated VSMCs. Thus, perivascular administration of MSCs may improve restenosis after vascular injury through paracrine effects that modulate VSMC inflammatory phenotype. Local MSC therapy suppressed neointimal formation after arterial injury in rats. Local MSC therapy modulated VSMC phenotype after arterial injury. MSC-secreted factors prevented VSMC proliferation and altered the phenotype.
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影响因子：
20.3
作者：
Sato, Kazuya;Ozaki, Katsutoshi;Ozawa, Keiya
通讯作者：
Ozawa, Keiya
影响因子：
4
作者：
Shimada, Issei S.;Spees, Jeffrey L.
通讯作者：
Spees, Jeffrey L.
影响因子：
5.2
作者：
Iso, Yoshitaka;Rao, Krithika S.;Poole, Charla N.;Zaman, A. K. M. Tarikuz;Curril, Ingrid;Sobel, Burton E.;Kajstura, Jan;Anversa, Piero;Spees, Jeffrey L.
通讯作者：
Spees, Jeffrey L.
影响因子：
6
作者：
Iso, Yoshitaka;Yamaya, Sayaka;Suzuki, Hiroshi
通讯作者：
Suzuki, Hiroshi
影响因子：
5
作者：
Sato, Takatoshi;Iso, Yoshitaka;Suzuki, Hiroshi
通讯作者：
Suzuki, Hiroshi