Insulin-like growth factor promotes engraftment, differentiation, and functional improvement after transfer of embryonic stem cells for myocardial restoration
Insulin-like growth factor promotes engraftment, differentiation, and functional improvement after transfer of embryonic stem cells for myocardial restoration
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DOI：
10.1634/stemcells.2004-0127
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发表时间：
2004-01-01
期刊：
影响因子：
5.2
通讯作者：
Robbins, RC
中科院分区：
文献类型：
--
作者：
Kofidis, T;de Bruin, JL;Robbins, RC
胰岛素样生长因子-1（IGF-1）促进心肌细胞增殖，并在胎儿早期给予时可逆转心脏异常。补充小鼠胚胎干细胞（ESC）悬浮液与IGF-1可能会增强细胞植入和宿主器官特异性分化后，注射在急性心肌损伤的区域。在这里报道的研究中，我们试图通过向注射的细胞群中添加IGF-1来增强ESCs在受损心脏中的恢复作用。将绿色荧光蛋白（GFP）标记的sv 129 ESC（2.5 × 10（5））注射到BalbC小鼠左前降支（LAD）动脉结扎后的缺血区域。在注射前将重组小鼠IGF-1（25 ng）加入细胞悬液中（n = 5）。2周后在器官收获前进行超声心动图检查。评价恢复程度（GFP（+）与梗死面积的比率）、GFP（+）细胞的心脏标志物表达、炎症反应和致瘤性。仅LAD结扎的小鼠（n = 5）和无IGF-1的ESC转移的小鼠（n = 5）作为对照。胚胎干细胞形成有活力的移植物并改善心脏功能。IGF-1组的左心室壁厚度较高（p = 0.025）。在IGF治疗组中存在缩短分数更高的趋势。组织学分析表明，IGF-1促进α-肌节肌动蛋白（p = .015）和主要组织相容性复合物I类（p = .01）的表达。IGF不影响细胞对供体细胞的反应或致瘤性。IGF-1促进ESCs心肌细胞表型的表达可作为细胞移植心肌修复的辅助手段。
Insulin-like growth factor-1 (IGF-1) promotes myocyte proliferation and can reverse cardiac abnormalities when it is administered in the early fetal stage. Supplementation of a mouse embryonic stem cell (ESC) suspension with IGF-1 might enhance cellular engraftment and host organ-specific differentiation after injection in the area of acute myocardial injury. In the study reported here, we sought to enhance the restorative effect of ESCs in the injured heart by adding IGF-1 to the injected cell population. Green fluorescent protein (GFP)-labeled sv 129 ESCs (2.5 x 10(5)) were injected into the ischemic area after left anterior descending (LAD) artery ligation in BalbC mice. Recombinant mouse IGF-1 (25 ng) was added to the cell suspension prior to the injection (n = 5). Echocardiography was performed before organ harvest 2 weeks later. The degree of restoration (ratio of GFP(+) to infarct area), expression of cardiac markers by GFP(+) cells, inflammatory response, and tumorigenicity were evaluated. Mice with LAD ligation only (n = 5) and ESC transfer without IGF-1 (n = 5) served as controls. ESCs formed viable grafts and improved cardiac function. Left ventricular wall thickness was higher in the IGF-1 group (p = .025). There was a trend toward higher fractional shortening in the IGF-treated group. Histological analysis demonstrated that IGF-1 promoted expression of alpha-sarcomeric actin (p = .015) and major histocompatibility complex class I (p = .01). IGF did not affect the cellular response to the donor cells or tumorigenicity. IGF-1 promotes expression of cardiomyocyte phenotype in ESCs in vivo. It should be considered as an adjuvant to cell transfer for myocardial restoration.