Abstract
Transplantation of mesenchymal stem cells (MSCs) has emerged as a promising strategy for the treatment of myriad human disorders, including several neurological diseases. Superparamagnetic iron oxide nanoparticles (SPION) and fluorine nanoemulsion (19F) are characterized by low toxicity and good sensitivity, and, as such, are among the most frequently used cell-labeling agents. However, to date, their impact across the various populations of MSCs has not been comprehensively investigated. Thus, the impact of MRI tags (independent variable) has been set as a primary endpoint. The various populations of mouse MSCs in which the effect of tag was investigated consisted of (1) tissue of cell origin: bone marrow vs. adipose tissue; (2) age of donor: young vs. old; (3) cell culture conditions: hypoxic vs. normal vs. normal + ascorbic acid (AA); (4) exposure to acidosis: yes vs. no. The impact of those populations has been also analyzed and considered as secondary endpoints. The experimental readouts (dependent variables) included: (1) cell viability; (2) cell size; (3) cell doubling time; (4) colony formation; (5) efficiency of labeling; and (6) cell migration. We did not identify any impact of cell labeling for these investigated populations in any of the readouts. In addition, we found that the harsh microenvironment of injured tissue modeled by a culture of cells in a highly acidic environment has a profound effect on all readouts, and both age of donor and cell origin tissue also have a substantial influence on most of the readouts, while oxygen tension in the cell culture conditions has a smaller impact on MSCs. A detailed characterization of the factors that influence the quality of MSCs is vital to the proper pursuit of preclinical and clinical studies.