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心脏驻留基质细胞和成纤维细胞分泌组潜能的比较分析

Comparative analysis of the potential of the secretomes of cardiac resident stromal cells and fibroblasts.

作者信息

Lino Jhonatan Basso, Robert Anny Waloski, Stimamiglio Marco Augusto, de Aguiar Alessandra Melo

机构信息

Stem Cells Basic Biology Laboratory, Carlos Chagas Institute - FIOCRUZ/PR, Curitiba, Paraná, Brazil.

出版信息

IUBMB Life. 2023 Mar;75(3):196-206. doi: 10.1002/iub.2557. Epub 2021 Sep 30.

Abstract

The secretome of different cell types has been applied on in vitro and in vivo assays, indicating considerable therapeutic potential. However, the choice of the ideal cell type and culture conditions for obtaining the best set of soluble factors, as well as the assays to assess specific effects, remain subjects of vigorous debate. In this study, we used mass spectrometry to characterize the secretomes of ventricle derived-cardiac resident stromal cells (vCRSC) and human dermal fibroblasts (HDFs) and evaluate them in an effort to understand the niche specificity of biological responses toward different cellular behaviors, such as cell proliferation, adhesion, migration, and differentiation. It was interesting to note that the HDF and vCRSC secretomes were both able to induce proliferation and cardiac differentiation of H9c2 cells, as well as to increase the adhesion activity of H9c2 cells and human umbilical vein endothelial cells. Analysis of the secretome composition showed that the vCRSCs derived from different donors secreted a similar set of proteins. Despite the differences, almost half of the proteins identified in conditioned medium were common to both HDF and vCRSC. Consequently, a high number of common biological processes were identified in the secretomes of the two cell types, which could help to explain the similar results observed in the in vitro assays. We show that soluble factors secreted by both HDF and vCRSC are able to promote proliferation and differentiation of cardiomyoblasts in vitro. Our study indicates the possible use of vCRSC or HDF secretomes in acellular therapies for regenerative medicine.

摘要

不同细胞类型的分泌组已应用于体外和体内试验,显示出相当大的治疗潜力。然而,选择理想的细胞类型和培养条件以获得最佳的可溶性因子组合,以及评估特定效应的试验,仍然是激烈争论的主题。在本研究中,我们使用质谱法对源自心室的心脏驻留基质细胞(vCRSC)和人皮肤成纤维细胞(HDF)的分泌组进行表征,并对其进行评估,以了解针对不同细胞行为(如细胞增殖、粘附、迁移和分化)的生物反应的生态位特异性。值得注意的是,HDF和vCRSC的分泌组都能够诱导H9c2细胞的增殖和心脏分化,以及增加H9c2细胞和人脐静脉内皮细胞的粘附活性。分泌组组成分析表明,来自不同供体的vCRSC分泌了一组相似的蛋白质。尽管存在差异,但在条件培养基中鉴定出的几乎一半蛋白质在HDF和vCRSC中都是常见的。因此,在两种细胞类型的分泌组中鉴定出了大量共同的生物学过程,这有助于解释在体外试验中观察到的相似结果。我们表明,HDF和vCRSC分泌的可溶性因子都能够在体外促进心肌细胞的增殖和分化。我们的研究表明,vCRSC或HDF分泌组可能用于再生医学的无细胞治疗。

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