A Promising New Approach for the Treatment of Inflammatory Pain: Transfer of Stem Cell-Derived Tyrosine Hydroxylase-Positive Cells
Autor: | Zsuzsa Jenei-Lanzl, Mieczyslaw Gajda, Rainer H. Straub, Hubert Stangl, Gisela Segond von Banchet, Hans-Georg Schaible, Matthias Ebbinghaus |
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Rok vydání: | 2018 |
Předmět: |
Male
musculoskeletal diseases 0301 basic medicine medicine.medical_specialty Tyrosine 3-Monooxygenase Immunology Pain Arthritis Inflammation Mice 03 medical and health sciences Endocrinology Immune system Internal medicine medicine Animals Pain Management Cells Cultured Interleukin 4 Tyrosine hydroxylase Endocrine and Autonomic Systems Chemistry medicine.disease Mice Inbred C57BL Arginase Treatment Outcome 030104 developmental biology medicine.anatomical_structure Neurology Female Bone marrow medicine.symptom Stem cell Stem Cell Transplantation |
Zdroj: | Neuroimmunomodulation. 25:225-237 |
ISSN: | 1423-0216 1021-7401 |
DOI: | 10.1159/000495349 |
Popis: | 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. |
Databáze: | OpenAIRE |
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