Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction

Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction
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DOI:
10.1016/j.biomaterials.2015.05.005
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发表时间:
2015-08-01
期刊:
影响因子:
14
通讯作者:
Sluijter, Joost P. G.
Sluijter, Joost P. G.
中科院分区:
工程技术1区
文献类型:
--
作者:
Gaetani, Roberto;Feyen, Dries A. M.;Sluijter, Joost P. G.

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心脏细胞疗法受到与移植后不良植入和显著细胞死亡相关的限制。在这方面,离体组织工程是一种已被证明可以增加细胞保留和存活的工具。我们研究的目的是评估由透明质酸/明胶(HA/凝胶)基质中的人心脏源性祖细胞(hCMPCs)组成的3D打印贴片的治疗潜力。将hCMPC印刷在HA/凝胶基质(30 × 10(6)个细胞/ml)中,以形成由6个垂直印刷的层制成的生物复合物,其表面为2 × 2cm,厚度为400 μ m,其中它们保留了它们的活力、增殖和分化能力。将打印的生物复合物移植到心肌梗死(MI)的小鼠模型中。如MRI和组织学所示,补片的应用显著减少了不良重塑和心脏性能的保护。此外,基质支持hCMPC的长期体内存活和植入,其在4周随访期间表现出心脏和血管分化标志物的暂时增加。总的来说,我们开发了一种有效的转化方法来增强hCMPC在心脏中的递送和作用。(C)2015爱思唯尔有限公司版权所有。
Cardiac cell therapy suffers from limitations related to poor engraftment and significant cell death after transplantation. In this regard, ex vivo tissue engineering is a tool that has been demonstrated to increase cell retention and survival. The aim of our study was to evaluate the therapeutic potential of a 3D-printed patch composed of human cardiac-derived progenitor cells (hCMPCs) in a hyaluronic acid/gelatin (HA/gel) based matrix. hCMPCs were printed in the HA/gel matrix (30 x 10(6) cells/ml) to form a biocomplex made of six perpendicularly printed layers with a surface of 2 x 2 cm and thickness of 400 um, in which they retained their viability, proliferation and differentiation capability. The printed biocomplex was transplanted in a mouse model of myocardial infarction (MI). The application of the patch led to a significant reduction in adverse remodeling and preservation of cardiac performance as was shown by both MRI and histology. Furthermore, the matrix supported the long-term in vivo survival and engraftment of hCMPCs, which exhibited a temporal increase in cardiac and vascular differentiation markers over the course of the 4 week follow-up period. Overall, we developed an effective and translational approach to enhance hCMPC delivery and action in the heart. (C) 2015 Elsevier Ltd. All rights reserved.