Differential Effector Response of Amnion- and Adipose-Derived Mesenchymal Stem Cells to Inflammation; Implications for Intradiscal Therapy

Intervertebral disc degeneration (IVDD) is a progressive condition marked by inflammation and tissue destruction. The effector functions of mesenchymal stem cells (MSCs) make them an attractive therapy for patients with IVDD. While several sources of MSCs exist, the optimal choice for use in the inflamed IVD remains a significant question. Adipose (AD)- and amnion (AM)-derived MSCs have several advantages compared to other sources, however, no study has directly compared the impact of IVDD inflammation on their effector functions. Human MSCs were cultured in media with or without supplementation of interleukin-1{beta} and tumor necrosis factor- at concentrations produced by IVDD cells. MSC proliferation and production of pro- and anti-inflammatory cytokines were quantified following 24- and 48-hours of culture. Additionally, the osteogenic and chondrogenic potential of AD- and AM-MSCs was characterized via histology and biochemical analysis following 28 days of culture. In inflammatory culture, AM-MSCs produced significantly more anti-inflammatory IL-10 (p=0.004) and larger chondrogenic pellets (p=0.04) with greater percent area staining positively for glycosaminoglycan (p<0.001) compared to AD-MSCs. Conversely, AD-MSCs proliferated more resulting in higher cell numbers (p=0.048) and produced higher concentrations of pro-inflammatory cytokines PGE2 (p=0.030) and IL-1{beta} (p=0.010) compared to AM-MSCs. Additionally, AD-MSCs produced more mineralized matrix (p<0.001) compared to AM-MSCs. These findings begin to inform researchers and clinicians as to which MSC source may be optimal for different IVD therapies including those that may promote regeneration or fusion. Further study is warranted evaluating these cells in systems which recapitulate the nutrient- and oxygen-deprived environment of the degenerate IVD.