Human pericytes for ischemic heart repair.
Human pericytes for ischemic heart repair.
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DOI：
10.1002/stem.1285
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发表时间：
2013-02
期刊：
影响因子：
5.2
通讯作者：
Huard, Johnny
中科院分区：
文献类型：
--
作者：
Chen, Chien-Wen;Okada, Masaho;Proto, Jonathan D.;Gao, Xueqin;Sekiya, Naosumi;Beckman, Sarah A.;Corselli, Mirko;Crisan, Mihaela;Saparov, Arman;Tobita, Kimimasa;Peault, Bruno;Huard, Johnny
人类微血管周细胞（CD 146 +/34−/45−/56−）含有多能前体，并修复/再生有缺陷的组织，特别是骨骼肌。然而，它们修复缺血心脏的能力仍然未知。我们研究了从骨骼肌中纯化的人周细胞治疗小鼠缺血性心脏病和介导相关修复机制的治疗潜力。超声心动图显示，周细胞移植减弱左心室扩张，并显着改善心肌收缩力，上级的CD 56+肌源性祖细胞移植，在急性梗死小鼠心脏。周细胞治疗显著减少心肌纤维化，并显著减少梗死部位宿主炎性细胞的浸润。体外低渗周细胞条件培养基抑制小鼠成纤维细胞增殖和抑制巨噬细胞增殖。除MCP-1外，周细胞的免疫调节分子，包括IL-6、LIF、考克斯-2和HMOX-1的高表达在缺氧下持续。宿主血管生成显著增加。周细胞在体内支持微血管结构，并在三维共培养物中与/不与内皮细胞形成毛细血管样网络。缺氧条件下，周细胞VEGF-A、PDGF-β、TGF-β1及其受体的表达显著增加，而bFGF、HGF、EGF和Ang-1的表达受到抑制。GFP标记揭示了周细胞分化成心肌细胞和/或与心肌细胞融合的能力，尽管程度很小。总之，心肌内移植纯化的人周细胞促进功能和结构的恢复，归因于多种机制，涉及旁分泌效应和细胞相互作用。
Human microvascular pericytes (CD146+/34−/45−/56−) contain multipotent precursors and repair/regenerate defective tissues, notably skeletal muscle. However, their ability to repair the ischemic heart remains unknown. We investigated the therapeutic potential of human pericytes, purified from skeletal muscle, for treating ischemic heart disease and mediating associated repair mechanisms in mice. Echocardiography revealed that pericyte transplantation attenuated left ventricular dilatation and significantly improved cardiac contractility, superior to CD56+ myogenic progenitor transplantation, in acutely infarcted mouse hearts. Pericyte treatment substantially reduced myocardial fibrosis and significantly diminished infiltration of host inflammatory cells at the infarct site. Hypoxic pericyte-conditioned medium suppressed murine fibroblast proliferation and inhibited macrophage proliferation in vitro. High expression by pericytes of immunoregulatory molecules, including IL-6, LIF, COX-2 and HMOX-1, was sustained under hypoxia, except for MCP-1. Host angiogenesis was significantly increased. Pericytes supported microvascular structures in vivo and formed capillary-like networks with/without endothelial cells in three-dimensional co-cultures. Under hypoxia, pericytes dramatically increased expression of VEGF-A, PDGF-β, TGF-β1 and corresponding receptors while expression of bFGF, HGF, EGF, and Ang-1 was repressed. The capacity of pericytes to differentiate into and/or fuse with cardiac cells was revealed by GFP-labeling, though to a minor extent. In conclusion, intramyocardial transplantation of purified human pericytes promotes functional and structural recovery, attributable to multiple mechanisms involving paracrine effects and cellular interactions.
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影响因子：
14
作者：
He, Wei;Nieponice, Alejandro;Soletti, Lorenzo;Hong, Yi;Gharaibeh, Burhan;Crisan, Mihaela;Usas, Arvydas;Peault, Bruno;Huard, Johnny;Wagner, William R.;Vorp, David A.
通讯作者：
Vorp, David A.
影响因子：
20.1
作者：
Katare R;Riu F;Mitchell K;Gubernator M;Campagnolo P;Cui Y;Fortunato O;Avolio E;Cesselli D;Beltrami AP;Angelini G;Emanueli C;Madeddu P
通讯作者：
Madeddu P
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
37.8
作者：
Campagnolo P;Cesselli D;Al Haj Zen A;Beltrami AP;Kränkel N;Katare R;Angelini G;Emanueli C;Madeddu P
通讯作者：
Madeddu P
影响因子：
21.3
作者：
Dellavalle, Arianna;Sampaolesi, Maurilio;Cossu, Giulio
通讯作者：
Cossu, Giulio