Role of host tissues for sustained humoral effects after endothelial progenitor cell transplantation into the ischemic heart.
Role of host tissues for sustained humoral effects after endothelial progenitor cell transplantation into the ischemic heart.
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DOI：
10.1084/jem.20070166
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发表时间：
2007-12-24
期刊：
影响因子：
--
通讯作者：
Yoon YS
中科院分区：
文献类型：
--
作者：
Cho HJ;Lee N;Lee JY;Choi YJ;Ii M;Wecker A;Jeong JO;Curry C;Qin G;Yoon YS
非细胞分化效应已成为介导干细胞或祖细胞移植治疗效果的重要机制。在这里，我们研究了骨髓（BM）来源的内皮祖细胞（EPC）移植到缺血心肌后体液因子的表达模式和来源及其局部和全身生物学效应。虽然大部分移植的EPCs在一周内消失，但多种体液因子的上调持续超过两周，这与心功能的恢复密切相关。为了确定体液因子的来源，我们将人类 EPC 注射到免疫缺陷小鼠体内。人 EPC（供体）来源的细胞因子的表达在一周内迅速降至不可检测的水平，而小鼠（受体）来源的细胞因子（包括可动员 BM 细胞的因子）则持续上调。在组织学上，我们观察到更高的毛细血管密度、更高的心肌细胞增殖、更低的心肌细胞凋亡和更小的梗塞面积。此外，EPC移植后，外周循环中骨髓来源的干细胞或祖细胞增加，并进入新血管形成和心肌修复部位。这些数据表明，心肌EPC移植可诱导体液效应，该效应由宿主组织维持，在修复心肌损伤中发挥至关重要的作用。
Noncellular differentiation effects have emerged as important mechanisms mediating therapeutic effects of stem or progenitor cell transplantation. Here, we investigated the expression patterns and sources of humoral factors and their regional and systemic biological effects after bone marrow (BM)-derived endothelial progenitor cell (EPC) transplantation into ischemic myocardium. Although most of the transplanted EPCs disappeared within a week, up-regulation of multiple humoral factors was sustained for longer than two weeks, which correlated well with the recovery of cardiac function. To determine the source of the humoral factors, we injected human EPCs into immunodeficient mice. Whereas the expression of human EPC (donor)-derived cytokines rapidly decreased to a nondetectable level within a week, up-regulation of mouse (recipient)-derived cytokines, including factors that could mobilize BM cells, was sustained. Histologically, we observed higher capillary density, a higher proliferation of myocardial cells, a lower cardiomyocyte apoptosis, and reduced infarct size. Furthermore, after EPC transplantation, BM-derived stem or progenitor cells were increased in the peripheral circulation and incorporated into the site of neovascularization and myocardial repair. These data indicate that myocardial EPC transplantation induces humoral effects, which are sustained by host tissues and play a crucial role in repairing myocardial injury.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
64.8
作者：
Murry, CE;Soonpaa, MH;Field, LJ
通讯作者：
Field, LJ
影响因子：
82.9
作者：
Kocher, AA;Schuster, MD;Itescu, S
通讯作者：
Itescu, S
DOI：
10.1084/jem.193.9.1005
发表时间：
2001-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hattori K;Dias S;Heissig B;Hackett NR;Lyden D;Tateno M;Hicklin DJ;Zhu Z;Witte L;Crystal RG;Moore MA;Rafii S
通讯作者：
Rafii S
影响因子：
11.4
作者：
Asahara, T;Takahashi, T;Isner, JM
通讯作者：
Isner, JM