Carmona M Dolores, Cañadillas Sagrario, Romero Miguel, Blanco Alfonso, Nogueras Sonia, Herrera Concha
Maimonides Institute of Biomedical Research in Cordoba (IMIBIC), Spain; Cellular Therapy Unit, Reina Sofia University Hospital, Cordoba, Spain; University of Cordoba, Spain.
Maimonides Institute of Biomedical Research in Cordoba (IMIBIC), Spain; Cellular Therapy Unit, Reina Sofia University Hospital, Cordoba, Spain; University of Cordoba, Spain.
Cytotherapy. 2017 Aug;19(8):947-961. doi: 10.1016/j.jcyt.2017.05.006. Epub 2017 Jun 30.
Effects of cell therapy on dilated cardiomyopathy (DCM) have been investigated in pre-clinical models using distinct cellular types in each study. A single study that compares the effectiveness of different cells is lacking.
We have compared the effects of intramyocardial injection (IMI) of bone marrow (BM)-derived mononuclear cells (MNCs), BM and adipose tissue (AT) mesenchymal stromal cells (BM-MSCs and AT-MSCs) on heart function, histological changes and myocardial ultrastructure in a rat model of DCM. Isogenic Wistar rats were used to isolate the different cell types and to induce DCM by autoimmune myocarditis. Animals were randomly assigned to receive BM-MNCs, BM-MSCs, AT-MSCs or placebo at day 42 by IMI. Serial echocardiography was used to assess cardiac function and hearts obtained after sacrifice at day 70, were used for histological and ultrastructural analysis. Serum levels of type B-natriuretic peptide (BNP) and vascular endothelial growth-factor (VEGF) were determined at different time points.
BM-MSC treatment induced significant improvement in ejection fraction (EF), fractional shortening (FS), left ventricular systolic diameter (LVESD) and systolic volume (LVESV). In contrast, changes in echocardiographic parameters with respect to pre-treatment values in animals receiving placebo, AT-MSCs or BM-MNCs were not statistically significant. EF and FS in animals receiving AT-MSCs were superior to those receiving placebo. BM-MSC transplantation induced also improvement in cardiac fibers organization and capillary density, fibrotic tissue reduction, increase in final VEGF concentration and BNP decrease.
IMI of BM or AT-MSCs improves LV function and induces more angiogenesis processes than BM-MNCs. In addition, BM-MSCs showed more anti-fibrotic effects and more ability to reorganize myocardial tissue compared with the other cell types.
在临床前模型中，每项研究都使用不同的细胞类型来研究细胞疗法对扩张型心肌病（DCM）的影响。目前缺乏一项比较不同细胞有效性的研究。
我们比较了在DCM大鼠模型中，经心肌注射（IMI）骨髓（BM）来源的单核细胞（MNCs）、BM和脂肪组织（AT）间充质基质细胞（BM-MSCs和AT-MSCs）对心脏功能、组织学变化和心肌超微结构的影响。使用同基因的Wistar大鼠分离不同的细胞类型，并通过自身免疫性心肌炎诱导DCM。在第42天，通过IMI将动物随机分配接受BM-MNCs、BM-MSCs、AT-MSCs或安慰剂。连续超声心动图用于评估心脏功能，在第70天处死动物后获取心脏，用于组织学和超微结构分析。在不同时间点测定血清B型利钠肽（BNP）和血管内皮生长因子（VEGF）水平。
BM-MSC治疗可显著改善射血分数（EF）、缩短分数（FS）、左心室收缩直径（LVESD）和收缩末期容积（LVESV）。相比之下，接受安慰剂、AT-MSCs或BM-MNCs的动物，超声心动图参数相对于治疗前值的变化无统计学意义。接受AT-MSCs的动物的EF和FS优于接受安慰剂的动物。BM-MSC移植还可改善心肌纤维组织和毛细血管密度，减少纤维化组织，提高最终VEGF浓度并降低BNP。
与BM-MNCs相比，BM或AT-MSCs的IMI可改善左心室功能并诱导更多的血管生成过程。此外，与其他细胞类型相比BM-MSCs显示出更强的抗纤维化作用和重组心肌组织的能力。
