衰老小鼠心脏中心脏球来源细胞移植后心脏功能无改善。
Lack of Cardiac Improvement After Cardiosphere-Derived Cell Transplantation in Aging Mouse Hearts.
机构信息
From the Institute for Cardiovascular Science and Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College (Z.-A.Z., X.H., W.L., J.L., Z.Y., J.W., X.-A.L., Y.C., S.H.), Soochow University, Suzhou, China.
Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Medical College (Z.-A.Z., X.H., W.L., J.L., Y.C., S.H.), Soochow University, Suzhou, China.
出版信息
Circ Res. 2018 Oct 26;123(10):e21-e31. doi: 10.1161/CIRCRESAHA.118.313005.
RATIONALE
Aging is one of the most significant risk factors for cardiovascular diseases, and the incidence of myocardial ischemia increases dramatically with age. Some studies have reported that cardiosphere-derived cells (CDCs) could benefit the injured heart. Nevertheless, the convincing evidence on CDC-induced improvement of aging heart is still limited.
OBJECTIVE
In this study, we tested whether the CDCs isolated from neonatal mice could benefit cardiac function in aging mice.
METHODS AND RESULTS
We evaluated cardiac function of PBS- (n=15) and CDC-injected (n=19) aging mice. Echocardiography indicated that left ventricular (LV) ejection fraction (57.46%±3.57% versus 57.86%±2.44%) and LV fraction shortening (30.67%±2.41% versus 30.51%±1.78%) showed similar values in PBS- and CDC-injected mice. The diastolic wall thickness of LV was significantly increased after CDC injection, resulting in reduced diastolic LV volume. The pulse-wave Doppler and tissue Doppler imaging indicated that aging mice receiving PBS or CDC injection presented similar values of the peak early transmitral flow velocity, the peak late transmitral flow velocity, the ratio of the peak early transmitral flow velocity to the peak late transmitral flow velocity, and the ratio of the peak early transmitral flow velocity to the peak early diastolic mitral annular velocity, respectively. Pressure-volume loop experiment indicated that the LV end-diastolic pressure-volume relationship and end-systolic pressure-volume relationship were comparable in both PBS- and CDC-injected mice. Postmortem analysis of aging mouse hearts showed similar fibrotic degree in the 2 groups. In addition, the aging markers showed comparable expression levels in both PBS- and CDC-injected mice. The systemic aging performance measures, including exercise capacity, hair regrowth capacity, and inflammation, showed no significant improvement in CDC-injected mice. Finally, the telomere length was comparable between PBS- and CDC-injected mice.
CONCLUSIONS
Together, these results indicate that CDCs do not improve heart function and systemic performances in aging mice.
背景
衰老是心血管疾病最重要的危险因素之一，随着年龄的增长，心肌缺血的发生率显著增加。一些研究表明，心肌球源性细胞（cardiosphere-derived cells，CDCs）有益于受损的心脏。然而，CDC 改善衰老心脏的确切证据仍然有限。
目的
本研究旨在测试从新生小鼠中分离的 CDCs 是否有益于衰老小鼠的心脏功能。
方法和结果
我们评估了 PBS（n=15）和 CDC 注射（n=19）的衰老小鼠的心脏功能。超声心动图显示，左心室（LV）射血分数（57.46%±3.57%对 57.86%±2.44%）和 LV 缩短分数（30.67%±2.41%对 30.51%±1.78%）在 PBS 和 CDC 注射的小鼠中具有相似的值。注射 CDC 后，LV 舒张壁厚度增加，导致 LV 舒张容积减少。脉冲波多普勒和组织多普勒成像显示，接受 PBS 或 CDC 注射的衰老小鼠具有相似的峰值早期二尖瓣血流速度、峰值晚期二尖瓣血流速度、峰值早期二尖瓣血流速度与峰值晚期二尖瓣血流速度之比以及峰值早期二尖瓣血流速度与峰值早期二尖瓣环速度之比。压力-容积环实验表明，LV 舒张末期压力-容积关系和收缩末期压力-容积关系在 PBS 和 CDC 注射的小鼠中相似。衰老小鼠心脏的死后分析显示两组的纤维化程度相似。此外，在 PBS 和 CDC 注射的小鼠中，衰老标志物的表达水平相似。CDC 注射的小鼠在运动能力、毛发再生能力和炎症等全身衰老表现指标上没有明显改善。最后，PBS 和 CDC 注射的小鼠端粒长度相似。
结论
综上所述，这些结果表明，CDCs 不能改善衰老小鼠的心脏功能和全身表现。
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