Department of Biohybrid & Medical Textiles, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany; Vermont Lung Center, University of Vermont, Burlington, Vermont, USA; Aachen-Maastricht Institute for Biobased Materials, Faculty of Science and Engineering, Maastricht University, Geleen, the Netherlands.
Vermont Lung Center, University of Vermont, Burlington, Vermont, USA; Department of Experimental Medical Sciences, Lund University, Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
Cytotherapy. 2021 Apr;23(4):293-300. doi: 10.1016/j.jcyt.2020.12.010. Epub 2021 Jan 29.
Cell-based therapies of pulmonary diseases with mesenchymal stromal cells (MSCs) are increasingly under experimental investigation. In most of these, MSCs are administered intravenously or by direct intratracheal instillation. A parallel approach is to administer the cells into the lung by endoscopic atomization (spraying). In a previous study, the authors developed a flexible endoscopic atomization device that allows administration of respiratory epithelial cells in the lungs with high survival.
In this study, the authors evaluated the feasibility of spraying MSCs with two different endoscopic atomization devices (air and pressure atomization). Following atomization, cell viability was evaluated with live/dead staining. Subsequent effects on cytotoxicity, trilineage differentiation and expression of MSC-specific markers as well as on MSC metabolic activity and morphology were analyzed for up to 7 days.
MSC viability immediately after spraying and subsequent metabolic activity for 7 days was not influenced by either of the devices. Slightly higher cytotoxicity rates could be observed for pressure-atomized compared with control and air-atomized MSCs over 7 days. Flow cytometry revealed no changes in characteristic MSC cell surface marker expression, and morphology remained unchanged. Standard differentiation into osteocytes, chondrocytes and adipocytes was inducible after atomization.
In the literature, a minimal survival of 50% was previously defined as the cutoff value for successful cell atomization. This is easily met with both of the authors' devices, with more than 90% survival. Thus, there is a potential role for atomization in intrapulmonary MSC-based cell therapies, as it is a feasible and easily utilizable approach based on clinically available equipment.
用间充质基质细胞（MSCs）进行基于细胞的肺部疾病治疗正在越来越多地受到实验研究。在这些研究中，大多数通过静脉内或直接经气管内滴注给予 MSC。另一种并行的方法是通过内镜雾化（喷雾）将细胞递送到肺部。在先前的研究中，作者开发了一种灵活的内镜雾化装置，允许将呼吸上皮细胞以高存活率递送到肺部。
在这项研究中，作者评估了使用两种不同的内镜雾化装置（空气和压力雾化）对 MSCs 进行喷雾的可行性。喷雾后，用活/死染色评估细胞活力。随后分析了细胞毒性、三系分化和 MSC 特异性标志物表达以及 MSC 代谢活性和形态的后续影响，最长可达 7 天。
喷雾后即刻和随后的 7 天代谢活性不受任何设备的影响。与对照和空气雾化 MSC 相比，压力雾化 MSC 在 7 天内的细胞毒性率略高。流式细胞术显示 MSC 特征细胞表面标志物表达无变化，形态保持不变。喷雾后可诱导 MSC 标准分化为成骨细胞、软骨细胞和脂肪细胞。
在文献中，先前定义了 50%的最小存活率作为成功细胞雾化的截止值。这两种作者的设备都很容易达到，存活率超过 90%。因此，雾化在基于 MSC 的肺内细胞治疗中具有潜在作用，因为它是一种基于临床可用设备的可行且易于使用的方法。
