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Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals.
Dong, Y, Bai, J, Zhang, Y, Zhou, Y, Pan, X, Li, X, Zhou, Q, Chen, Y, Lai, M, Mao, B, et al
Journal of leukocyte biology. 2020;(6):1711-1725
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Abstract
Antagonism of ROS signaling can inhibit cell apoptosis and autophagy, thus favoring the maintenance and expansion of hematopoietic stem cells. Alpha lipoic acid (ALA), a small antioxidant molecule, affects cell apoptosis by lowering the ROS level. In this study, we show that ALA promoted production of human pluripotent stem cells (hPSCs) derived hemogenic endothelial cells and hematopoietic stem/progenitor cells in vitro. Transcriptome analysis of hPSCs derived hemogenic endothelial cells showed that ALA promoted endothelial-to-hematopoietic transition by up-regulating RUNX1, GFI1, GFI1B, MEIS2, and HIF1A and down-regulating SOX17, TGFB1, TGFB2, TGFB3, TGFBR1, and TGFBR2. ALA also up-regulated sensor genes of ROS signals, including HIF1A, FOXO1, FOXO3, ATM, PETEN, SIRT1, and SIRT3, during the process of hPSCs derived hemogenic endothelial cells generation. However, in more mature hPSC-derived hematopoietic stem/progenitor cells, ALA reduced ROS levels and inhibited apoptosis. In particular, ALA enhanced development of hPSCs derived hematopoietic stem/progenitor cells by up-regulating HIF1A in response to a hypoxic environment. Furthermore, addition of ALA in ex vivo culture greatly improved the maintenance of functional cord blood HSCs by in vivo transplantation assay. Our findings support the conjecture that ALA plays an important role in efficient regeneration of hematopoietic stem/progenitor cells from hPSCs and maintenance of functional HSCs, providing insight into understanding of regeneration of early hematopoiesis for engineering clinically useful hPSCs derived hematopoietic stem/progenitor cells transplantation. Thus, ALA can be used in the study of hPSCs derived HSCs.
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Curative Effects of Valsartan Alone or Combined with Alpha-lipoic Acid on Inflammatory Cytokines and Renal Function in Early-stage Diabetic Kidney Disease.
Jiang, Z, Tan, Z, Meng, F, Li, X
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2019;(10):1009-1011
Abstract
The aim of this study was to compare curative effects of valsartan alone or combined with alpha-lipoic acid (ALA) on inflammatory cytokine indices including hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and renal function indices including urinary albumin excretion rate (UAER), β2-microglobulin (β2-MG) and cystatin C (Cys C) of patients with early-stage diabetic kidney disease (DKD). One hundred and two patients with early-stage DKD were randomly divided into group A and group B, with 51 patients in each group. Group A was administered with valsartan alone, while group B was administered with valsartan combined with ALA. Research showed that 14 days after treatment, group B had significantly lowered hs-CRP, TNF-α, UAER, β2-MG and Cys C when compared with group A (all p<0.001). Compared to valsartan alone, valsartan combined with ALA can reduce level of inflammatory cytokines in serum and improve renal function.