Effect of α-lipoic Acid on Immunosuppressive Effect of Human Umbilical Cord Mesenchymal Stem Cells
Zhang Jie, Yao Huan, Wu Mengyun, Li Yasha, Yang Ke*
Nuclear factor erythroid 2-related factor 2 (NRF2) is a key molecule of antioxidative stress in cells. Activation of NRF2 could effectively reverse the senescence phenotype of stem cells. The purpose of the study was to investigate the role of α-lipoic acid (ALA), an agonist of NRF2, in promoting immunosuppression ability of umbilical cord mesenchymal stem cells (UC-MSCs). P5 and P18 UC-MSCs were cultured, cell proliferation and senescence phenotype were detected by β-gal staining, CCK-8 and immunofluorescence. Western blot was used to detect the expression of senescence-associated protein p16 and NRF2 signaling pathway-related molecules NRF2 and pS40-NRF2. Real-time quantitative PCR was used to detect the difference of mRNA expression of indoleamine 2,3-dioxygenase 1 (IDO-1), which is the cellular immunomodulatory inhibitory factor. Flow cytometry was used to detect the difference in the ability of UC-MSCs to inhibit peripheral blood mononuclear cell (PBMC) proliferation. The results showed that after long-term amplification in vitro, UC-MSCs showed senescence phenotype and their proliferative ability decreased; the protein expression of NRF2 and pS40-NRF2 was decreased; the mRNA expression level of IFN-γ-resistant IDO-1 was decreased significantly, and their ability of inhibiting PBMC proliferation was decreased. After UC-MSCs treated by ALA, the number of β-gal staining positive cells was decreased and cell proliferation was promoted. The expression of IDO-1 was increased and the ability of inhibiting PBMC proliferation was promoted. We concluded that ALA can delay the aging of UC-MSCs and enhance UCMSCs immunosuppressive ability.
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