Dai Wangde, Hale Sharon L, Kloner Robert A
The Heart Institute, Good Samaritan Hospital, Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90017-2395, USA.
Regen Med. 2007 Jan;2(1):63-8. doi: 10.2217/17460751.2.1.63.
We aimed to determine whether soluble factors released by cultured mesenchymal stem cells (MSCs) improved cardiac function in an experimental model of myocardial infarction.
MSCs were cultured in fresh medium. The conditioned medium, which contained factors secreted by MSCs, was collected after 4 days of culture. Fischer rats with 1-week-old myocardial infarction were divided into four groups that received: saline (n = 12); fresh medium (n = 10); conditioned medium (n = 8); or 2 million MSCs in fresh medium (n = 10) by direct intramyocardial injection. A total of 4 weeks later, left ventricular (LV) function was assessed by LV angiogram and by LV catheterization. Hearts were processed for histology.
Before treatment, LV angiogram assessment demonstrated that the baseline LV function was comparable among the four groups. At 4 weeks after treatment, LV angiogram and LV catheterization showed that LV ejection fraction was better in the fresh medium (49.5 +/- 1.0%), conditioned medium (48.5 +/- 2.1%) and MSCs groups (49.9 +/- 4.2%) than in the saline group (43.7 +/- 1.2%; p < 0.05). There were no significant differences in heart rate, blood pressure, postmortem LV volume, infarct size or septum thickness among the groups. The scar thickness was similar in the saline (395 +/- 31 microm), fresh medium (404 +/- 30 microm) and conditioned medium (397 +/- 34 microm) groups, but significantly thicker in the MSCs group (560 +/- 51 microm; p < 0.05).
Fresh medium, conditioned medium and MSC injection all improved LV function at 4 weeks after treatment compared with saline treatment in a rat myocardial infarct model; only MSCs increased wall thickness. Since the culture medium contains nutrients and bovine serum, the roles of the soluble factors released by MSCs might be masked. The effect of these nutrients needs further investigation.
我们旨在确定培养的间充质干细胞（MSC）释放的可溶性因子是否能改善心肌梗死实验模型中的心脏功能。
将MSC培养于新鲜培养基中。培养4天后收集含有MSC分泌因子的条件培养基。将1周龄心肌梗死的Fischer大鼠分为四组，分别通过直接心肌内注射接受：生理盐水（n = 12）；新鲜培养基（n = 10）；条件培养基（n = 8）；或新鲜培养基中200万个MSC（n = 10）。共4周后，通过左心室（LV）血管造影和LV导管插入术评估左心室（LV）功能。对心脏进行组织学处理。
治疗前，LV血管造影评估显示四组之间的基线LV功能相当。治疗后4周，LV血管造影和LV导管插入术显示，新鲜培养基组（49.5±1.0%）、条件培养基组（48.5±2.1%）和MSC组（49.9±4.2%）的LV射血分数优于生理盐水组（43.7±1.2%；p<0.05）。各组之间的心率、血压、死后LV容积、梗死面积或室间隔厚度无显著差异。生理盐水组（395±31微米）、新鲜培养基组（404±30微米）和条件培养基组（397±34微米）的瘢痕厚度相似，但MSC组明显更厚（560±51微米；p<0.05）。
在大鼠心肌梗死模型中，与生理盐水治疗相比，新鲜培养基、条件培养基和MSC注射在治疗后4周均改善了LV功能；只有MSC增加了壁厚。由于培养基含有营养物质和牛血清，MSC释放的可溶性因子的作用可能被掩盖。这些营养物质的作用需要进一步研究。
