Mesenchymal stem cells (MSC) secrete neuroprotective molecules that may be useful as an alternative to cell transplantation itself. Our purpose was to develop different pharmaceutical compositions based on conditioned medium (CM) of adipose MSC (aMSC) stimulated by and/or combined with nicotinamide (NIC), vasoactive intestinal peptide (VIP), or both factors; and to evaluate in vitro their proliferative and neuroprotective potential. Nine pharmaceutical compositions were developed from 3 experimental approaches: (1) unstimulated aMSC-CM collected and combined with NIC, VIP, or both factors (NIC+VIP), referred to as the aMSC-CM combined composition; (2) aMSC-CM collected just after stimulation with the mentioned factors and containing them, referred to as the aMSC-CM stimulated-combined composition; and (3) aMSC-CM previously stimulated with the factors, referred to as the aMSC stimulated composition. The potential of the pharmaceutical compositions to increase cell proliferation under oxidative stress and neuroprotection were evaluated in vitro by using a subacute oxidative stress model of retinal pigment epithelium cells (line ARPE-19) and spontaneous degenerative neuroretina model. Results showed that oxidatively stressed ARPE-19 cells exposed to aMSC-CM stimulated and stimulated-combined with NIC or NIC+VIP tended to have better recovery from the oxidative stress status. Neuroretinal explants cultured with aMSC-CM stimulated-combined with NIC+VIP had better preservation of the neuroretinal morphology, mainly photoreceptors, and a lower degree of glial cell activation. In conclusion, aMSC-CM stimulated-combined with NIC+VIP contributed to improving the proliferative and neuroprotective properties of the aMSC secretome. Further studies are necessary to evaluate higher concentrations of the drugs and to characterize specifically the aMSC-secreted factors related to neuroprotection. However, this study supports the possibility of improving the potential of new effective pharmaceutical compositions based on the secretome of MSC plus exogenous factors or drugs without the need to inject cells into the eye, which can be very useful in retinal pathologies.

中文翻译：

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烟酰胺和血管活性肠肽增强间充质干细胞分泌组：视网膜退行性疾病的一种新的治疗方法。

间充质干细胞（MSC）分泌神经保护分子，可以用作细胞移植本身的替代物。我们的目的是基于受烟酰胺（NIC），血管活性肠肽（VIP）或这两种因素刺激和/或与之结合的脂肪MSC（aMSC）的条件培养基（CM）开发不同的药物组合物；并进行体外评估它们的增殖和神经保护潜力。从3种实验方法中开发出9种药物组合物：（1）收集未刺激的aMSC-CM并与NIC，VIP或这两种因素（NIC + VIP）组合，称为aMSC-CM组合组合物；（2）用上述因子刺激后立即收集并含有它们的aMSC-CM，称为aMSC-CM刺激的组合物；（3）先前用所述因子刺激的aMSC-CM，称为aMSC刺激的组合物。在体外评估了药物组合物在氧化应激和神经保护下增加细胞增殖的潜力。通过使用视网膜色素上皮细胞（线ARPE-19）的亚急性氧化应激模型和自发性变性神经视网膜模型。结果表明，氧化应激的ARPE-19细胞暴露于aMSC-CM刺激下并与NIC或NIC + VIP结合刺激，具有从氧化应激状态中恢复的趋势。用MSC + CM刺激的NIC + VIP结合培养的神经视网膜外植体具有更好的神经视网膜形态保存，主要是感光细胞，并且胶质细胞活化程度较低。总之，与NIC + VIP刺激结合的aMSC-CM有助于改善aMSC分泌组的增殖和神经保护特性。有必要进行进一步的研究以评估药物的更高浓度并明确表征与神经保护有关的aMSC分泌因子。