联合心肌内递送人周细胞和心脏干细胞通过刺激血管和肌肉修复，可累加改善小鼠梗死心脏的愈合。
Combined intramyocardial delivery of human pericytes and cardiac stem cells additively improves the healing of mouse infarcted hearts through stimulation of vascular and muscular repair.
机构信息
From the Experimental Cardiovascular Medicine (E.A., H.L.S., F.R., R.K., G.M., A.O., I.R.-A., Z.D., K.M., C.R., V.V.A., J.R., P.M.) and Vascular Pathology and Regeneration (M.M., C.E.), School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; Institute of Cardiovascular and Medical Sciences (M.M.), University of Glasgow, Glasgow, United Kingdom; Department of Physiology, University of Otago, Dunedin, New Zealand (R.K.); Department of Medical and Biological Sciences (D.C., A.P.B.) and Department of Experimental Medical and Clinical Sciences (U.L.), University of Udine, Udine, Italy; and Cardiac Surgery, Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom (G.A.).
出版信息
Circ Res. 2015 May 8;116(10):e81-94. doi: 10.1161/CIRCRESAHA.115.306146. Epub 2015 Mar 23.
RATIONALE
Optimization of cell therapy for cardiac repair may require the association of different cell populations with complementary activities.
OBJECTIVE
Compare the reparative potential of saphenous vein-derived pericytes (SVPs) with that of cardiac stem cells (CSCs) in a model of myocardial infarction, and investigate whether combined cell transplantation provides further improvements.
METHODS AND RESULTS
SVPs and CSCs were isolated from vein leftovers of coronary artery bypass graft surgery and discarded atrial specimens of transplanted hearts, respectively. Single or dual cell therapy (300 000 cells of each type per heart) was tested in infarcted SCID (severe combined immunodeficiency)-Beige mice. SVPs and CSCs alone improved cardiac contractility as assessed by echocardiography at 14 days post myocardial infarction. The effect was maintained, although attenuated at 42 days. At histological level, SVPs and CSCs similarly inhibited infarct size and interstitial fibrosis, SVPs were superior in inducing angiogenesis and CSCs in promoting cardiomyocyte proliferation and recruitment of endogenous stem cells. The combination of cells additively reduced the infarct size and promoted vascular proliferation and arteriogenesis, but did not surpass single therapies with regard to contractility indexes. SVPs and CSCs secrete similar amounts of hepatocyte growth factor, vascular endothelial growth factor, fibroblast growth factor, stem cell factor, and stromal cell-derived factor-1, whereas SVPs release higher quantities of angiopoietins and microRNA-132. Coculture of the 2 cell populations results in competitive as well as enhancing paracrine activities. In particular, the release of stromal cell-derived factor-1 was synergistically augmented along with downregulation of stromal cell-derived factor-1-degrading enzyme dipeptidyl peptidase 4.
CONCLUSIONS
Combinatory therapy with SVPs and CSCs may complementarily help the repair of infarcted hearts.
理由
优化细胞疗法治疗心脏修复可能需要不同细胞群体与互补活性的结合。
目的
在心肌梗死模型中比较大隐静脉来源的周细胞（SVPs）与心脏干细胞（CSCs）的修复潜能，并研究联合细胞移植是否能提供进一步的改善。
方法和结果
SVPs 和 CSCs 分别从冠状动脉旁路移植术遗留的静脉和移植心脏废弃的心房标本中分离出来。将单种或两种细胞治疗（每种细胞 30 万）应用于心肌梗死的 SCID（严重联合免疫缺陷）-Beige 小鼠。单独使用 SVPs 和 CSCs 可改善心肌梗死后 14 天的超声心动图评估的心脏收缩功能。这种作用在 42 天仍然存在，尽管有所减弱。在组织学水平上，SVPs 和 CSCs 同样抑制梗死面积和间质纤维化，SVPs 在诱导血管生成方面优于 CSCs，而 CSCs 在促进心肌细胞增殖和招募内源性干细胞方面优于 SVPs。细胞联合治疗可附加地减少梗死面积，并促进血管增殖和动脉生成，但在收缩功能指标方面并不优于单一疗法。SVPs 和 CSCs 分泌的肝细胞生长因子、血管内皮生长因子、成纤维细胞生长因子、干细胞因子和基质细胞衍生因子-1 的量相似，而 SVPs 释放的血管生成素和 microRNA-132 的量较高。两种细胞群体的共培养会产生竞争和增强的旁分泌活性。特别是，基质细胞衍生因子-1 的释放协同增强，同时基质细胞衍生因子-1 降解酶二肽基肽酶 4 的表达下调。
结论
SVPs 和 CSCs 的联合治疗可能互补地有助于修复梗死的心脏。
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