The multifactorial complexity of spinal cord injuries includes the formation of a glial scar, of which chondroitin sulphated proteoglycans (CSPG) are an integral component. Previous studies have shown CSPG to have inhibitory effects on endothelial and neuronal cell growth, highlighting the difficulty of spinal cord regeneration. Mesenchymal stem/stromal cells (MSC) are widely used a cell therapy, and there is mounting evidence for their angiogenic and neurotrophic paracrine properties. However, in vivo studies have observed poor engraftment and survival of MSC when injected into SCI. Currently, it is not known whether increasing CSPG concentrations seen after SCI may affect MSC; therefore we have investigated the effects of CSPG exposure to MSC in vitro. CSPG-mediated inhibition of MSC adhesion was observed when MSC where cultured on substrates of increasing CSPG concentration, however MSC viability was not affected even up to five days of culture. Culture conditioned medium harvested from these cultures (primed MSC CM) was used as both culture substrata and soluble medium for EA. hy926 endothelial cells and SHSY5Y neuronal cells. MSC CM was angiogenic, promoting endothelial cell adhesion, proliferation and tubule formation. However, exposing MSC to CSPG reduced the effects of CSPG-primed MSC CM on endothelial cell adhesion and proliferation, but did not reduce MSC-induced endothelial tubule formation. Primed MSC CM also promoted neuronal cell adhesion, which was reduced following exposure to CSPG. There were no marked differences in neurite outgrowth in MSC CM from CSPG primed MSC cultures versus control conditions, although non-primed MSC CM from the same donors was found to significantly enhance neurite outgrowth. Taken together, these studies demonstrate that MSC are resilient to CSPG exposure, but that there is a marked effect of CSPG on their paracrine regenerative activity. The findings increase our understanding of how the wound microenvironment after SCI can mitigate the beneficial effects of MSC transplantation.

脊髓损伤的多因素复杂性包括神经胶质瘢痕的形成，其中硫酸软骨素蛋白多糖（CSPG）是其中不可或缺的组成部分。先前的研究表明CSPG对内皮细胞和神经元细胞的生长具有抑制作用，突显了脊髓再生的困难。间充质干/基质细胞（MSC）被广泛用于细胞治疗，并且其血管生成和神经营养性旁分泌特性得到越来越多的证据。但是，体内研究发现，当注入SCI时，MSC的植入率和存活率都很差。目前，尚不清楚在SCI后CSPG浓度升高是否会影响MSC。因此，我们研究了CSPG体外暴露于MSC的影响。当将MSC培养在CSPG浓度增加的底物上时，观察到CSPG介导的MSC粘附抑制，但是即使在培养5天之内，MSC的生存能力也没有受到影响。从这些培养物中收获的培养条件培养基（灌注的MSC CM）既用作EA的培养基，又用作可溶性培养基。hy926内皮细胞和SHSY5Y神经元细胞。MSC CM具有血管生成作用，可促进内皮细胞粘附，增殖和小管形成。但是，将MSC暴露于CSPG会降低CSPG引发的MSC CM对内皮细胞粘附和增殖的影响，但不会减少MSC诱导的内皮小管形成。引发的MSC CM还促进神经元细胞粘附，接触CSPG后神经细胞粘附减少。尽管发现来自相同供体的未灌注MSC CM显着增强了神经突的生长，但CSPG灌注的MSC培养物中的MSC CM的神经突生长与对照条件没有显着差异。综上所述，这些研究表明，MSC具有抗CSPG暴露的能力，但是CSPG对其旁分泌的再生活性具有显着的影响。这些发现增加了我们对SCI后伤口微环境如何减轻MSC移植的有益作用的了解。