The low engraftment and retention rate of mesenchymal stem cells (MSCs) at the target site indicates that the potential benefits of MSC-based therapies can be attributed to their paracrine signaling. In this study, the extracellular matrices (ECMs) deposited by bone marrow-derived human MSCs in the presence and absence of ascorbic acid was characterized. MSCs were seeded on top of decellularized ECM (dECM) and the concentrations of proangiogenic and antiangiogenic molecules released in culture (conditioned) media was compared. Effects of ECM derived from MSCs with different passage numbers on MSC secretome was also investigated. Our study revealed that the expression of proangiogenesis-related factors were upregulated when MSCs were harvested on dECMs, irrespective of media supplementation, as compared with those cultured on tissue culture plates. In addition, dECM generated in the presence of ascorbic acid promoted the expression of proangiogenic molecules as compared with dECM-derived in absence of media supplementation. Further, it was observed that the effectiveness of dECM to stimulate proangiogenic signaling of MSCs was reduced as cell passage number was increased from P3 to P5. The proliferation as well as capillary morphogenesis of human umbilical vein endothelial cells (HUVECs) in the presence of conditioned media were enhanced compared with the normal HUVECs culture media. These data indicate that the secretory signatures of MSCs and consequently, the therapeutic efficacy of MSCs can be regulated by presentation of dECM composition and variation of its composition.

中文翻译：

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利用间充质干细胞分泌基因组：细胞外基质对促血管生成信号的影响。

间充质干细胞（MSCs）在目标部位的低植入率和保留率表明基于MSC的疗法的潜在益处可归因于其旁分泌信号传导。在这项研究中，在存在和不存在抗坏血酸的情况下，对源自骨髓的人MSC沉积的细胞外基质（ECM）进行了表征。将MSC接种在脱细胞的ECM（dECM）上，比较培养基（条件培养基）中释放的促血管生成和抗血管生成分子的浓度。还研究了来自具有不同传代次数的MSC的ECM对MSC分泌组的影响。我们的研究表明，与在组织培养板上培养的培养基相比，在dECMs上收获MSC时，与培养基添加无关，其促血管生成相关因子的表达上调。另外，与在不添加培养基的情况下衍生的dECM相比，在抗坏血酸存在下产生的dECM促进了促血管生成分子的表达。此外，观察到随着细胞传代次数从P3增加到P5，dECM刺激MSC的促血管生成信号的有效性降低。与正常HUVECs培养基相比，在条件培养基下，人脐静脉内皮细胞（HUVECs）的增殖和毛细血管形态发生均得到增强。这些数据表明，MSC的分泌特征以及因此的MSC的治疗功效可以通过呈现dECM组成和其组成的变化来调节。与不添加培养基的情况下衍生的dECM相比，在抗坏血酸存在下产生的dECM促进了促血管生成分子的表达。此外，观察到随着细胞传代次数从P3增加到P5，dECM刺激MSC的促血管生成信号的有效性降低。与正常HUVECs培养基相比，在条件培养基下，人脐静脉内皮细胞（HUVECs）的增殖和毛细血管形态发生均得到增强。这些数据表明，MSC的分泌特征以及因此的MSC的治疗功效可以通过呈递dECM组成和其组成变化来调节。与不添加培养基的情况下衍生的dECM相比，在抗坏血酸存在下产生的dECM促进了促血管生成分子的表达。此外，观察到随着细胞传代次数从P3增加到P5，dECM刺激MSC的促血管生成信号的有效性降低。与正常HUVECs培养基相比，在条件培养基下，人脐静脉内皮细胞（HUVECs）的增殖和毛细血管形态发生均得到增强。这些数据表明，MSC的分泌特征以及因此的MSC的治疗功效可以通过呈现dECM组成和其组成的变化来调节。观察到，随着细胞传代次数从P3增加到P5，dECM刺激MSCs促血管生成信号的有效性降低。与正常HUVECs培养基相比，在条件培养基下，人脐静脉内皮细胞（HUVECs）的增殖和毛细血管形态发生均得到增强。这些数据表明，MSC的分泌特征以及因此的MSC的治疗功效可以通过dECM组成的呈现及其组成的变化来调节。观察到，随着细胞传代次数从P3增加到P5，dECM刺激MSCs促血管生成信号的有效性降低。与正常HUVECs培养基相比，在条件培养基下，人脐静脉内皮细胞（HUVECs）的增殖和毛细血管形态发生均得到增强。这些数据表明，MSC的分泌特征以及因此的MSC的治疗功效可以通过呈递dECM组成和其组成变化来调节。