alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population

We present here the data showing, in standard cultures exposed to atmospheric O-2 concentration, that alpha-tocopherol acetate (alpha-TOA) has a positive impact on primitive cells inside mesenchymal stromal cell (MstroC) population, by maintaining their proliferative capacity. alpha-TOA decreases the O-2 consumption rate of MStroC probably by impacting respiratory chain complex II activity. This action, however, is not associated with a compensatory increase in glycolysis activity, in spite of the fact that the degradation of HIF-1 alpha was decreased in presence of alpha-TOA. This is in line with a moderate enhancement of mtROS upon alpha-TOA treatment. However, the absence of glycolysis stimulation implies the inactivity of HIF-1 alpha which might - if it were active - be related to the maintenance of stemness. It should be stressed that alpha-TOA might act directly on the gene expression as well as the mtROS themselves, which remains to be elucidated.This is the peer reviewed version of the paper: Loncarić, D., Rodriguez, L., Debeissat, C., Touya, N., Labat, V., Villacreces, A., Bouzier-Sore, A.-K., Pasquet, J.-M., de la Grange, P. B., Vlaski-Lafarge, M., Pavlović, S., & Ivanović, Z. (2021). Alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population. Stem Cell Reviews and Reports, 17(4), 1390–1405.[ https://doi.org/10.1007/s12015-020-10111-9]Related to published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/1491

Alpha Lipoic-Acid Potentiates Ex Vivo Expansion of Human Steady-State Peripheral Blood Hematopoietic Primitive Cells

Steady state peripheral blood (SSPB) contains hematopoietic stem and progenitor cells (HSPCs) presenting characteristics of real hematopoietic stem cells, and thus represents an interesting alternative cell supply for hematopoietic cell transplantation. Development of ex vivo expansion strategies could overcome the low HSPC numbers usually rescued from SSPB. We investigated the effect of alpha lipoic acid (ALA) on ex vivo culture of SSPB CD34 positive (CD34pos) cells on primitive cell expansion, cell cycle, and oxidative metabolism as estimated by determining the ROS and GSH content. ALA increased the ex vivo expansion of total CD34pos cells and of phenotypically defined CD34pos HSPCs subpopulations that retained in vivo repopulating capacity, concomitantly to a decreased expansion of differentiating cells. ALA did not modify cell cycle progression nor the proliferation of ex vivo expanded CD34pos cells, and coherently did not affect the ROS level. On the contrary, ALA decreased the proliferation and disturbed cell cycle progression of cells reaching a differentiated status, a phenomenon that seems to be associated with a drop in ROS level. Nonetheless, ALA affected the redox status of hematopoietic primitive cells, as it reproducibly increased GSH content. In conclusion, ALA represents an interesting molecule for the improvement of ex vivo expansion strategies and further clinical application in hematopoietic cell transplantation (HCT)

Repopulating Hematopoietic Stem Cells From Steady-State Blood Before And After Ex Vivo Culture Are Enriched In CD34+CD133+CXCR4low Fraction

The feasibility of ex vivo expansion allows us to consider the steady-state peripheral blood as an alternative source of hematopoietic stem progenitor cells for transplantation when growth factor-induced cell mobilization is contraindicated or inapplicable. Ex vivo expansion dramatically enhances the in vivo reconstituting cell population from steady-state blood. In order to investigate phenotype and the expression of homing molecules, the expression of CD34, CD133, CD90, CD45RA, CD26 and CD9 was determined on sorted CD34+ cells according to CXCR4 (“neg”, “low” “bright”) and CD133 expression before and after ex vivo expansion. Hematopoietic stem cell activity was determined in vivo on the basis of hematopoietic repopulation of primary and secondary recipients - NSG immuno-deficient mice. In vivo reconstituting cells in the steady-state blood CD34+ cell fraction before expansion belong to the CD133+ population and are CXCR4low or, to a lesser extent, CXCR4neg, while after ex vivo expansion they are contained only in the CD133+CXCR4low cells. The failure of the CXCR4bright population to engraft is probably due to the exclusive expression of CD26 by these cells. The limiting-dilution analysis showed that both repopulating cell number and individual proliferative capacity were enhanced by ex vivo expansion. Thus, steady-state peripheral blood cells exhibit a different phenotype compared to mobilized and cord blood cells, as well as to those issued from the bone marrow. These data represent the first phenotypic characterization of steady-state blood cells exhibiting short- and long-term hematopoietic reconstituting potential, which can be expanded ex vivo, a sine qua non for their subsequent use for transplantation.publishedVersionCopyright © 2018 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcod

α-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population

We present here the data showing, in standard cultures exposed to atmospheric O-2 concentration, that alpha-tocopherol acetate (alpha-TOA) has a positive impact on primitive cells inside mesenchymal stromal cell (MstroC) population, by maintaining their proliferative capacity. alpha-TOA decreases the O-2 consumption rate of MStroC probably by impacting respiratory chain complex II activity. This action, however, is not associated with a compensatory increase in glycolysis activity, in spite of the fact that the degradation of HIF-1 alpha was decreased in presence of alpha-TOA. This is in line with a moderate enhancement of mtROS upon alpha-TOA treatment. However, the absence of glycolysis stimulation implies the inactivity of HIF-1 alpha which might - if it were active - be related to the maintenance of stemness. It should be stressed that alpha-TOA might act directly on the gene expression as well as the mtROS themselves, which remains to be elucidated

Meeting report of the 4th biennial Metabolism and Cancer symposium

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