水动力喷射递送无足迹 iPSC 衍生心肌细胞到猪心肌。

Hydrojet-based delivery of footprint-free iPSC-derived cardiomyocytes into porcine myocardium.

机构信息

Department of Thoracic and Cardiovascular Surgery, University Hospital Tuebingen, Calwerstraße 7/1, 72076, Tuebingen, Germany.

Erbe Elektromedizin Tuebingen, Waldhoernlestr. 17, 72072, Tuebingen, Germany.

出版信息

Sci Rep. 2020 Oct 8;10(1):16787. doi: 10.1038/s41598-020-73693-x.

Abstract

The reprogramming of patient´s somatic cells into induced pluripotent stem cells (iPSCs) and the consecutive differentiation into cardiomyocytes enables new options for the treatment of infarcted myocardium. In this study, the applicability of a hydrojet-based method to deliver footprint-free iPSC-derived cardiomyocytes into the myocardium was analyzed. A new hydrojet system enabling a rapid and accurate change between high tissue penetration pressures and low cell injection pressures was developed. Iron oxide-coated microparticles were ex vivo injected into porcine hearts to establish the application parameters and the distribution was analyzed using magnetic resonance imaging. The influence of different hydrojet pressure settings on the viability of cardiomyocytes was analyzed. Subsequently, cardiomyocytes were delivered into the porcine myocardium and analyzed by an in vivo imaging system. The delivery of microparticles or cardiomyocytes into porcine myocardium resulted in a widespread three-dimensional distribution. In vitro, 7 days post-injection, only cardiomyocytes applied with a hydrojet pressure setting of E20 (79.57 ± 1.44%) showed a significantly reduced cell viability in comparison to the cells applied with 27G needle (98.35 ± 5.15%). Furthermore, significantly less undesired distribution of the cells via blood vessels was detected compared to 27G needle injection. This study demonstrated the applicability of the hydrojet-based method for the intramyocardial delivery of iPSC-derived cardiomyocytes. The efficient delivery of cardiomyocytes into infarcted myocardium could significantly improve the regeneration.

摘要

将患者体细胞重编程为诱导多能干细胞(iPSCs),并进一步分化为心肌细胞,为治疗梗死心肌提供了新的选择。在这项研究中,分析了基于水力喷射的方法将无足迹的 iPSC 衍生心肌细胞递送到心肌中的适用性。开发了一种新的水力喷射系统,能够在高组织穿透压力和低细胞注射压力之间快速准确地切换。用氧化铁涂层的微颗粒对猪心进行离体注射,以确定应用参数,并使用磁共振成像分析其分布。分析了不同水力喷射压力设置对心肌细胞活力的影响。随后,将心肌细胞递送到猪心肌中,并使用体内成像系统进行分析。微颗粒或心肌细胞递送到猪心肌中会导致广泛的三维分布。在体外,注射后 7 天,与用 27G 针(98.35±5.15%)施加的细胞相比,用 E20(79.57±1.44%)水力喷射压力设置施加的细胞活力显著降低。此外,与 27G 针注射相比,通过血管输送细胞的不良分布明显减少。这项研究证明了基于水力喷射的方法在心肌内递送 iPSC 衍生的心肌细胞的适用性。将心肌细胞有效递送到梗死心肌中,可以显著改善心肌再生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f26/7546722/bac4b458c379/41598_2020_73693_Fig1_HTML.jpg

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