Transplantation of adipose-derived stem cells combined with neuregulin-microparticles promotes efficient cardiac repair in a rat myocardial infarction model
Transplantation of adipose-derived stem cells combined with neuregulin-microparticles promotes efficient cardiac repair in a rat myocardial infarction model
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DOI：
10.1016/j.jconrel.2017.01.026
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发表时间：
2017-03-10
影响因子：
10.8
通讯作者：
Jose Blanco-Prieto, Maria
中科院分区：
文献类型：
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作者：
Diaz-Herraez, Paula;Saludas, Laura;Jose Blanco-Prieto, Maria
组织工程是促进心肌梗死（MI）后心脏再生的一种很有前途的策略。在这项研究中，我们在大鼠心肌梗死模型上研究了脂肪来源干细胞（ADSCs）与装载神经调节蛋白（NRG）的微粒（MPs）相结合的系统的修复潜力，称为ADSC-NRG-MPs。首先，将细胞附着在包裹NRG的MPs表面，并用胶原蛋白和聚d -赖氨酸的1:1混合物包被。体内给药一周后，该系统有利于巨噬细胞表达从促炎表型转变为再生表型。从长期来看，ADSCs与MPs的粘附导致细胞植入增加，在组织中可检测到细胞长达3个月。与此相一致的是，用附着于MPs的细胞处理的动物的组织修复效果更好，其左心室比单独用ADSCs处理的动物更厚。此外，NRG在系统中的存在促进了更完全的再生，减少梗死面积并刺激心肌细胞增殖。在血管生成方面，与对照组相比，单独存在ADSCs和NRG-MPs刺激血管形成，但两者联合诱导的血管生成作用最大，促进了小动脉和毛细血管的形成。重要的是，只有当ADSCs粘附在MPs上时，它们才被纳入新形成的血管。总的来说，这些发现表明，ADSCs、MPs和NRG的结合有利于促进心脏再生的更大、更彻底的改善，并为该策略的临床前研究提供了强有力的证据。(C) 2017 Elsevier B.V.版权所有
Tissue engineering is a promising strategy to promote heart regeneration after a myocardial infarction (MI). In this study, we investigated the reparative potential of a system that combines adipose-derived stem cells (ADSCs) with microparticles (MPs) loaded with neuregulin (NRG), named ADSC-NRG-MPs, on a rat MI model. First, cells were attached to the surface of MPs encapsulating NRG and coated with a 1:1 mixture of collagen and poly-D-lysine. One week after in vivo administration, the system favored the shift of macrophage expression from a pro-inflammatory to a regenerative phenotype. At long-term, the adhesion of ADSCs to MPs resulted in an increased cell engraftment, with cells being detectable in the tissue up to three months. In consonance, better tissue repair was observed in the animals treated with cells attached to MPs, which presented thicker left ventricles than the animals treated with ADSCs alone. Moreover, the presence of NRG in the system promoted a more complete regeneration, reducing the infarct size and stimulating cardiomyocyte proliferation. Regarding vasculogenesis, the presence of ADSCs and NRG-MPs alone stimulated vessel formation when compared to the control group, but the combination of both induced the largest vasculogenic effect, promoting the formation of both arterioles and capillaries. Importantly, only when ADSCs were administered adhered to MPs, they were incorporated into newly formed vessels. Collectively, these findings demonstrate that the combination of ADSCs, MPs and NRG favored a synergy for inducing a greater and more complete improvement in heart regeneration and provided strong evidence to move forward with preclinical studies with this strategy. (C) 2017 Elsevier B.V. All rights reserved.