Apolipoprotein A-I Supports MSCs Survival under Stress Conditions

Abstract

Clinical trials have shown the safety of mesenchymal stem/stromal cells (MSCs) transplantation, but the effectiveness of these treatments is limited. Since, transplanted MSCs will undergo metabolic disturbances in the bloodstream, we investigated the influence of blood plasmas of type 2 diabetes (T2D) patients on MSCs viability and examined whether apolipoprotein A-I (apoA-I) could protect cells from stressful conditions of serum deprivation (SD), hypoxia, and elevated concentrations of reactive oxygen species (ROS). ApoA-I exhibits anti-inflammatory, immune activities, improves glycemic control, and is suitable for T2D patients but its influence on MSCs remains unknown. For the first time we have shown that apoA-I decreases intracellular ROS and supports proliferative rate of MSCs, thereby increasing cell count in oxidation conditions. ApoA-I did not influence cell cycle when MSCs were predominantly in the G0/G1 phases under conditions of SD/hypoxia, activated proliferation rapidly, and reduced apoptosis during MSCs transition to the oxygenation or oxidation conditions. Finally, it was found that the blood plasma of T2D individuals had a cytotoxic effect on MSCs in 39% of cases and had a wide variability of antioxidant properties. ApoA-I protects cells under all adverse conditions and can increase the efficiency of MSCs transplantation in T2D patients.

Angiogenin Levels and Their Association with Cardiometabolic Indices Following Vitamin D Status Correction in Saudi Adults

“…Apo-AI clearly induces apoptosis by lowering angiogenin production in order to reduce anti-stress function. This indicates that apo-AI not only controls cholesterol homeostasis in the brain, but also has a role in protecting the brain from injury and stress [ 39 ]. The current study contrastingly showed positive correlations between the level of ANG and apo-AI at the baseline, probably reflecting the absence of pathological conditions in the enrolled patients.…”

Apolipoprotein-A is a potential prognostic biomarker for severe aplastic anemia patients treated with ATG-based immunosuppressive therapy: a single-center retrospective study

“…In addition to its role in cholesterol trafficking, Apo-A, a multifunctional protein, participates in inflammatory and immune responses [27]. It also stimulates the proliferation of monocytes, granulocytes and their progenitor cells and bone marrow MSCs [28] and supports MSC survival under stress conditions [29], which might be beneficial for hematopoiesis recovery [20]. Some studies revealed that exogenousfree Apo-A alters the characteristics of progenitor cell populations [30].…”

Therapeutic Potential of Mesenchymal Stem Cells in a Pre-Clinical Model of Diabetic Kidney Disease and Obesity

“…In that way, further studies with MSC administration associated with glycemic control in the BTBR ob/ob mice will significantly improve the metabolic and renal therapeutic effects, halting DKD progression and more precisely simulating clinical translational application. Furthermore, it will be a great opportunity to investigate MSCs’ reparative mechanisms in a glucose-controlled setting, which can protect administered cells and enhance their therapeutic effectiveness [ 64 ].…”