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大型动物模型中心包内间充质干细胞给药:生物分布分析

Intrapericardial administration of mesenchymal stem cells in a large animal model: a bio-distribution analysis.

作者信息

Blázquez Rebeca, Sánchez-Margallo Francisco Miguel, Crisóstomo Verónica, Báez Claudia, Maestre Juan, García-Lindo Mónica, Usón Alejandra, Álvarez Verónica, Casado Javier G

机构信息

Stem Cell Therapy Unit, Minimally Invasive Surgery Centre, Caceres, Spain.

Endoluminal Therapy and Diagnosis, Minimally Invasive Surgery Centre, Caceres, Spain.

出版信息

PLoS One. 2015 Mar 27;10(3):e0122377. doi: 10.1371/journal.pone.0122377. eCollection 2015.

Abstract

The appropriate administration route for cardiovascular cell therapy is essential to ensure the viability, proliferative potential, homing capacity and implantation of transferred cells. At the present, the intrapericardial administration of pharmacological agents is considered an efficient method for the treatment of cardiovascular diseases. However, only a few reports have addressed the question whether the intrapericardial delivery of Mesenchymal Stem Cells (MSCs) could be an optimal administration route. This work firstly aimed to analyze the pericardial fluid as a cell-delivery vehicle. Moreover, the in vivo biodistribution pattern of intrapericardially administered MSCs was evaluated in a clinically relevant large animal model. Our in vitro results firstly showed that, MSCs viability, proliferative behavior and phenotypic profile were unaffected by exposure to pericardial fluid. Secondly, in vivo cell tracking by magnetic resonance imaging, histological examination and Y-chromosome amplification clearly demonstrated the presence of MSCs in pericardium, ventricles (left and right) and atrium (left and right) when MSCs were administered into the pericardial space. In conclusion, here we demonstrate that pericardial fluid is a suitable vehicle for MSCs and intrapericardial route provides an optimal retention and implantation of MSCs.

摘要

心血管细胞治疗的合适给药途径对于确保移植细胞的活力、增殖潜力、归巢能力和植入至关重要。目前,心包内给药被认为是治疗心血管疾病的一种有效方法。然而,只有少数报告探讨了心包内递送间充质干细胞(MSCs)是否可能是一种最佳给药途径这一问题。这项工作首先旨在分析心包液作为一种细胞递送载体。此外,在一个临床相关的大型动物模型中评估了心包内给药的MSCs的体内生物分布模式。我们的体外结果首先表明,MSCs的活力、增殖行为和表型特征不受暴露于心包液的影响。其次,通过磁共振成像、组织学检查和Y染色体扩增进行的体内细胞追踪清楚地表明,当将MSCs注入心包腔时,心包、心室(左心室和右心室)和心房(左心房和右心房)中存在MSCs。总之,我们在此证明心包液是MSCs的合适载体,心包内途径能使MSCs实现最佳的留存和植入。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf8c/4376786/3fb901780884/pone.0122377.g001.jpg

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