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.
Highlights
Nowadays, mesenchymal stem/stromal cells (MSCs) have become an attractive tool for regenerative medicine due to their self-renewal, multilineage, and immunosuppressive capacities as well as the ease of their isolation by standard methods
The safety of introduced MSCs has been shown in several clinical trials but the effectiveness of treatment was limited owing to cell death during transplantation due to the harsh microenvironment within damaged recipients tissues [17,18,19]
The extraction of apolipoprotein A-I (apoA-I) from blood plasma by fractionation of high density lipoproteins (HDL), delipidation under non-denaturing conditions, with a mixture of butanol-isopropyl ether and gel filtration gives a protein with a purity of approximately 95% (Figure 1A) with a native structure, which is consistent with the further characterization of its secondary structure (Figure 1)
Summary
Mesenchymal stem/stromal cells (MSCs) have become an attractive tool for regenerative medicine due to their self-renewal, multilineage, and immunosuppressive capacities as well as the ease of their isolation by standard methods. Their capability to migrate and repair injured tissues and organs makes them a very promising tool for transplantation. Thanks to these properties, MSCs have been introduced in clinical trials for bone and cartilage regeneration [1,2] and the treatment of immune disorders [3,4], critical limb ischemia [5], bronchopulmonary dysplasia [6], type 2 diabetes (T2D) [7,8,9], type 1 diabetes [10], and heart disease [11,12]. Studies have shown heterogeneous results when MSCs are used to treat these diseases [20,21]
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