Oliveira E, Assunção-Silva R C, Ziv-Polat O, Gomes E D, Teixeira F G, Silva N A, Shahar A, Salgado A J
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
Stem Cells Int. 2017;2017:6319129. doi: 10.1155/2017/6319129. Epub 2017 Dec 3.
Mesenchymal stem cells (MSCs) have been proposed for spinal cord injury (SCI) applications due to their capacity to secrete growth factors and vesicles-secretome-that impacts important phenomena in SCI regeneration. To improve MSC survival into SCI sites, hydrogels have been used as transplantation vehicles. Herein, we hypothesized if different hydrogels could interact differently with adipose tissue-derived MSCs (ASCs). The efficacy of three natural hydrogels, gellan gum (functionalized with a fibronectin peptide), collagen, and a hydrogel rich in laminin epitopes (NVR-gel) in promoting neuritogenesis (alone and cocultured with ASCs), was evaluated in the present study. Their impact on ASC survival, metabolic activity, and gene expression was also evaluated. Our results indicated that all hydrogels supported ASC survival and viability, being this more evident for the functionalized GG hydrogels. Moreover, the presence of different ECM-derived biological cues within the hydrogels appears to differently affect the mRNA levels of growth factors involved in neuronal survival, differentiation, and axonal outgrowth. All the hydrogel-based systems supported axonal growth mediated by ASCs, but this effect was more robust in functionalized GG. The data herein presented highlights the importance of biological cues within hydrogel-based biomaterials as possible modulators of ASC secretome and its effects for SCI applications.
间充质干细胞（MSCs）因其分泌生长因子和囊泡分泌组的能力而被提议用于脊髓损伤（SCI）治疗，这些因子和分泌组会影响SCI再生中的重要现象。为提高MSCs在SCI部位的存活率，水凝胶已被用作移植载体。在此，我们假设不同的水凝胶与脂肪组织来源的间充质干细胞（ASCs）的相互作用是否会有所不同。本研究评估了三种天然水凝胶——结冷胶（用纤连蛋白肽功能化）、胶原蛋白以及富含层粘连蛋白表位的水凝胶（NVR - 凝胶）在促进神经突生长方面的效果（单独使用以及与ASCs共培养时）。还评估了它们对ASC存活、代谢活性和基因表达的影响。我们的结果表明，所有水凝胶都能支持ASC的存活和活力，这在功能化的结冷胶水凝胶中更为明显。此外，水凝胶中不同的细胞外基质衍生生物信号似乎对参与神经元存活、分化和轴突生长的生长因子的mRNA水平有不同影响。所有基于水凝胶的系统都支持由ASCs介导的轴突生长，但这种效果在功能化的结冷胶中更为显著。本文所呈现的数据凸显了基于水凝胶的生物材料中的生物信号作为ASC分泌组及其对SCI应用效果的可能调节剂的重要性。
