Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.

Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.
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DOI:
10.1371/journal.pone.0012077
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发表时间:
2010-08-10
期刊:
影响因子:
3.7
通讯作者:
Krieger JE
Krieger JE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Danoviz ME;Nakamuta JS;Marques FL;dos Santos L;Alvarenga EC;dos Santos AA;Antonio EL;Schettert IT;Tucci PJ;Krieger JE

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心脏细胞移植受到低细胞保留和差移植物活力的影响。在此,在心肌梗死(MI)大鼠模型中评价了联合注射脂肪组织来源的干细胞(ASC)和生物聚合物对细胞心脏滞留、心室形态和性能的影响。 MI后24小时,使用纤维蛋白a、胶原(ASC/C)或培养基(ASC/M)作为载体,注射从同基因刘易斯大鼠分离的99 mTc标记的ASC(1×106个细胞),24小时后通过收获器官的γ发射计数评估细胞体分布。ASC/F和ASC/C组在心肌中保留的细胞显著多于ASC/M组(分别为13.8±2.0和26.8±2.4%对4.8± 0.7%)。然后,在MI细胞注射后4周评价形态测量和直接心脏功能参数。与未处理组(NT)和对照组(仅培养基、纤维蛋白或胶原蛋白)相比,所有ASC处理组的左心室(LV)周长和备用心肌间质胶原蛋白百分比均显著减弱。药理学应激下的直接血流动力学评估显示,无论用于递送ASC的载体如何,ASC治疗组的每搏输出量(SV)和左心室舒张末期压均保持不变。心搏功(SW)是心脏功能的一个整体指数,ASC/M改善,而生物聚合物与ASC共注射时则正常化。在血流动力学应激下,观察到心脏ASC保留和SV保留与MI后SW改善之间呈正相关。我们提供了直接的证据表明,心肌内注射ASC减轻了大鼠MI后的负性心脏重塑并保留了心室功能,并且这些有益作用可以通过将ASC与生物聚合物共同注射而进一步增强。
Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). 99mTc-labeled ASCs (1×106 cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by γ-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8±2.0 and 26.8±2.4% vs. 4.8±0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administrating co-injection of ASCs with biopolymers.
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