Abstract

BackgroundAlzheimer's disease is usually diagnosed by significant extracellular deposition of beta-amyloid and intracellular neurofibrillary tangle formation. Here, we investigated the paracrine effect of amniotic fluid-derived mesenchymal stem cells on AD changes in human SH–SY5Y cells. MethodsSH–SY5Y cells were divided into five groups: Control, 0.1 µg/ml LPS, 10 µg/ml LPS, 0.1 µg/ml LPS + conditioned medium, and 10 µg/ml LPS + conditioned medium. Cells were incubated with 0.1% and 10 µg/ml LPS for 48 h, followed by incubation with the conditioned medium of amniotic fluid-derived mesenchymal stem cells for the next 24 h. Beta-amyloid plaques were monitored by Congo-red staining. Survival and apoptosis were assessed by the MTT assay and flow cytometric analysis of Annexin-V. ELISA was used to measure the levels of neprilysin, angiotensin-converting enzyme, and Matrix Metalloproteinase–9. A PCR array was used to measure the expression of genes involved in neurogenesis. ResultsBright-field imaging showed beta-amyloid plaques in the group treated with 10 µg/ml LPS. We found minimal effects in groups receiving 0.1 µg/ml LPS. The data showed that the reduction in the levels of neprilysin, angiotensin-converting enzyme, and Matrix Metalloproteinase–9 in the LPS-treated cells was attenuated after incubation with the stem cell secretome (p < 0.05). Amniotic fluid stem cell secretome increased the viability of LPS-treated SH–SY5Y cells (p 0.05) and was associated with a decrease in apoptotic changes (p < 0.05). We found the modulation of several genes involved in neurogenesis in the 10 µg/ml LPS + conditioned medium group compared to cells treated with 10 µg/ml LPS alone. ConclusionAmniotic fluid stem cell secretion reduces AD-like pathologies in the human neuronal lineage.

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