Cai Liying, Johnstone Brian H, Cook Todd G, Tan Jian, Fishbein Michael C, Chen Peng-Sheng, March Keith L
Indiana Center for Vascular Biology and Medicine, Indiana University School of Medicine, Indianapolis, USA.
Stem Cells. 2009 Jan;27(1):230-7. doi: 10.1634/stemcells.2008-0273.
The administration of therapeutic cell types, such as stem and progenitor cells, has gained much interest for the limitation or repair of tissue damage caused by a variety of insults. However, it is still uncertain whether the morphological and functional benefits are mediated predominantly via cell differentiation or paracrine mechanisms. Here, we assessed the extent and mechanisms of adipose-derived stromal/stem cells (ASC)-dependent tissue repair in the context of acute myocardial infarction. Human ASCs in saline or saline alone was injected into the peri-infarct region in athymic rats following left anterior descending (LAD) coronary artery ligation. Cardiac function and structure were evaluated by serial echocardiography and histology. ASC-treated rats consistently exhibited better cardiac function, by all measures, than control rats 1 month following LAD occlusion. Left ventricular (LV) ejection fraction and fractional shortening were improved in the ASC group, whereas LV remodeling and dilation were limited in the ASC group compared with the saline control group. Anterior wall thinning was also attenuated by ASC treatment, and post-mortem histological analysis demonstrated reduced fibrosis in ASC-treated hearts, as well as increased peri-infarct density of both arterioles and nerve sprouts. Human ASCs were persistent at 1 month in the peri-infarct region, but they were not observed to exhibit significant cardiomyocyte differentiation. Human ASCs preserve heart function and augment local angiogenesis and cardiac nerve sprouting following myocardial infarction predominantly by the provision of beneficial trophic factors.
诸如干细胞和祖细胞等治疗性细胞类型的应用,已因限制或修复由各种损伤导致的组织损伤而备受关注。然而,形态学和功能上的益处是否主要通过细胞分化或旁分泌机制介导仍不确定。在此,我们评估了脂肪来源的基质/干细胞(ASC)在急性心肌梗死情况下依赖的组织修复程度和机制。在左冠状动脉前降支(LAD)结扎后,将处于盐溶液中的人ASC或仅盐溶液注射到无胸腺大鼠的梗死周边区域。通过系列超声心动图和组织学评估心脏功能和结构。在LAD闭塞1个月后,通过所有指标评估,接受ASC治疗的大鼠心脏功能始终比对照大鼠更好。与盐溶液对照组相比,ASC组的左心室(LV)射血分数和缩短分数得到改善,而LV重塑和扩张受到限制。ASC治疗还减轻了前壁变薄,死后组织学分析表明,接受ASC治疗的心脏纤维化减少,梗死周边小动脉和神经芽的密度增加。人ASC在梗死周边区域1个月时仍持续存在,但未观察到它们表现出明显的心肌细胞分化。人ASC在心肌梗死后主要通过提供有益的营养因子来维持心脏功能并增强局部血管生成和心脏神经芽生。