A major impediment in the success of cell therapy for neurodegenerative diseases is the poor survival of grafted cells in the in vivo milieu, predominantly due to accumulated reactive oxygen species, thus prompting the search for suitable alternatives. Accumulating evidence suggests that the therapeutic potential of transplanted cells is partially attributed to the secretome released by them into the extracellular milieu. Studies that investigated the neuroprotective potential of the secretome attributes to the mere presence of growth factors without addressing other underlying cellular/molecular changes that occur upon post-secretome intervention like re-establishing the host cell’s free radical scavenging machineries. In the present study, we investigated the neuroprotective effects of human embryonic kidney (HEK-293) cell line derived secretome (HEK-S) in an in vitro model of kainic acid (KA) induced neurodegeneration and explored the possible neuroprotective mechanism(s) of HEK-S. Murine hippocampal cells were exposed to toxic doses of KA (200 μM) for 6 hours (H) or 24H to induce excitotoxicity. Kainic acid exposed hippocampal cells were then treated with HEK-S either simultaneously or 6 h post-KA exposure. Our results revealed that HEK-S confers significant neuroprotection in early/later stages of neurodegeneration through insulin like growth factor (IGF) – phosphatidylinositol-3-kinases (PI3 K) pathway, efficiently restoring the host’s free radical scavenging mechanisms at molecular-cellular-biochemical levels and also by modulating kainate receptor subunit expressions in host neurons.

神经退行性疾病细胞治疗成功的主要障碍是体内移植细胞的不良存活环境，主要是由于积累了活性氧，因此促使人们寻找合适的替代品。越来越多的证据表明，移植细胞的治疗潜力部分归因于它们释放到细胞外环境中的分泌组。研究了分泌组的神经保护潜力的研究仅归因于生长因子的存在，而没有解决分泌组干预后发生的其他潜在的细胞/分子变化，例如重建宿主细胞的自由基清除机制。在本研究中，我们在体外研究了人胚胎肾（HEK-293）细胞系分泌分泌蛋白（HEK-S）的神经保护作用。藻酸（KA）引起的神经变性的模型，并探讨了HEK-S可能的神经保护机制。将鼠海马细胞暴露于毒性剂量的KA（200μM）中6小时（H）或24H以诱导兴奋性毒性。暴露于海藻酸的海马细胞然后同时或暴露于KA后6小时用HEK-S处理。我们的结果表明，HEK-S通过胰岛素样生长因子（IGF）–磷脂酰肌醇3-激酶（PI3 K）途径在神经退行性病变的早期/后期赋予了重要的神经保护作用，从而有效地恢复了宿主在分子细胞内的自由基清除机制。生化水平以及通过调节宿主神经元中的红藻氨酸受体亚基表达。