Should the influence of pathological obesity be considered when using hASCs for tissue engineering applications?

INTRODUCTION. Some pathological condition, like obesity, may influence the features of human adipose-derived mesenchymal stem cells (hASCs). Indeed, adipose tissue of obese patients shows a reduced pressure of oxygen, involved in the up-regulation of pro-inflammatory genes that could affect the properties of these cells. MATERIALS AND METHODS. We have isolated hASCs from subcutaneous adipose tissue of normal-weight donors (nS-hASCs, n=5, mean age 33±6 years, BMI=24±2) and from pathological obese donors (ObS-hASCs, n=5, mean age 43±10 years, mean BMI=43±5). We have also collected visceral adipose tissue from the obese patients (ObV-hASCs, n=5) in order to evaluate possible differences in the expression of the cell inflammatory phenotype. We have characterized hASCs clonogenicity, immunophenotype and osteogenic potential. We have also evaluated the effects of hypoxic treatment on obese hASCs cells. RESULTS. The clonogenic potential of cell populations, is strongly lower in ObS-hASCs than in normal-weight patients (-51%), and it is greater in subcutaneous than in omental tissue among obese patients (+142%). ObS-hASCs show a significantly higher doubling time in comparison to nS-hASCs (+40%); moreover ObV-hASCs doubling time is higher than its corresponding subcutaneous cells (+29%). From the immunophenotipic point of view, the expression of CD54, CD90 and CD166 is significantly reduced in ObS-hASCs respect to normal-weight patients. The osteogenic potential of hASCs is also affected by obesity: indeed, a significant reduction in the alkaline phosphatase activity and calcified extracellular matrix deposition was observed. Preliminary data suggest that both ObS- and OBV-hASCs are responsive to hypoxic treatment resulting in the activation of pro-inflammatory genes. CONCLUSIONS. The pathological obesity negatively affects the self-maintaining and differentiation ability of hASCs, probably due to the inflammatory state related to this conditions. Our data suggest that some pathological condition should be considered before proposing the use of hASCs in tissue engineering applications.