A Promising New Approach for the Treatment of Inflammatory Pain: Transfer of Stem Cell-Derived Tyrosine Hydroxylase-Positive Cells

摘要

Objectives: The appearance of endogenous tyrosine hydroxylase-positive cells (TH+ cells) in collagen-induced arthritis was associated with an anti-inflammatory effect. Here we investigated putative anti-inflammatory and antinociceptive effects of the transfer of induced, bone marrow stem cell-derived TH+ cells (iTH(+) cells) on murine antigen-induced arthritis (AIA). Methods: Bone marrow-derived stem cells were differentiated into iTH(+) cells. These cells were transferred to mice immunized against methylated bovine serum albumin (mBSA) 2 days before AIA was induced by injection of mBSA into one knee joint. In AIA control mice and iTH(+)-treated mice the severity of AIA, pain-related behavior, humoral and cellular responses, and the invasion of macrophages into the dorsal root ganglia were assessed. Results: The intravenous transfer of iTH(+) cells before AIA induction did not cause a sustained suppression of AIA severity but significantly reduced inflammation-evoked pain-related behavior. The iTH(+) cells used for transfer exhibited enormous production of interleukin-4. A major difference between AIA control mice and iTH(+)-treated AIA mice was a massive invasion of the dorsal root ganglia by iNOS-negative, arginine 1-positive macrophages corresponding to an M2 phenotype. The differences in other cellular and humoral immune parameters such as release of cytokines from stimulated lymphocytes between AIA control mice and iTH(+)-treated mice were small. Conclusions: The transfer of iTH(+) cells may cause a long-lasting reduction of arthritis-induced pain even if it does not ameliorate inflammation. The invasion of M2 macrophages into the dorsal root ganglia is likely to be an important mechanism of antinociception. (C) 2018 S. Karger AG, Basel