Aging-related Decrease of Human ASC Angiogenic Potential Is Reversed by Hypoxia Preconditioning Through ROS Production

Abstract

Adipose stroma/stem cells (ASC) represent an ideal source of autologous cells for cell-based therapy. Their transplantation enhances neovascularization after experimental ischemic injury. Aging is associated with a progressive decrease in the regenerative potential of mesenchymal stem cells (MSCs) from bone marrow. This work aims to determine the aging effect on human ASC capacities. First, we show that aging impairs angiogenic capacities of human ASC (hASC) in a mouse ischemic hindlimb model. Although no change in hASC number, phenotype, and proliferation was observed with aging, several mechanisms involved in the adverse effects of aging have been identified in vitro combining a concomitant decrease in (i) ASC ability to differentiate towards endothelial cells, (ii) secretion of proangiogenic and pro-survival factors, and (iii) oxidative stress. These effects were counteracted by a hypoxic preconditioning that improved in vivo angiogenic capacities of hASC from older donors, while hASC from young donors that have a strong ability to manage hypoxic stress were not. Finally, we identified reactive oxygen species (ROS) generation as a key signal of hypoxia on hASC angiogenic capacities. This study demonstrates for the first time that age of donor impaired angiogenic capacities of hASC in ischemic muscle and change in ROS generation by hypoxic preconditioning reverse the adverse effect of aging.

Efficiency of Exosome Production Correlates Inversely with the Developmental Maturity of MSC Donor

“…Unlike the controversial embryonic stem cells, MSCs could be isolated from many ethically palatable tissues such as bone marrow [16,17], adipose tissue [17,18], liver [19,20], muscle [21,22], amniotic fluid [23,24], placenta [25,26], umbilical cord blood [16,27], dental pulp [28,29]. However, it is generally observed that the biological activity and therapeutic potency of MSCs correlate inversely with developmental stage of the donor [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. Therefore, MSCs from ethically and socially controversial but "young" tissues such as fetal tissues [49] and human embryonic stem cells (ESCs) [50] continue to be investigated for their therapeutic potential.…”

Neurophysiological Repercussions of Anabolic Steroid Abuse: A Road into Neurodegenerative Disorders

“…In physiological concentrations, testosterone and AS can slightly increase the concentration of ROS, which might induce neuronal preconditioning, protecting these cells against further increases in ROS concentration [96,97]. However, in supraphysiological concentrations, AS can significantly increase the ROS bioavailability by mitochondrial and nonmitochondrial mechanisms, resulting in oxidative damage and neuronal apoptosis.…”

Hypoxic Preconditioning of Stem Cells as a New Approach to Increase the Efficacy of Cell Therapy for Myocardial Infarction

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