A Promising New Approach for the Treatment of Inflammatory Pain: Transfer of Stem Cell-Derived Tyrosine Hydroxylase-Positive Cells
A Promising New Approach for the Treatment of Inflammatory Pain: Transfer of Stem Cell-Derived Tyrosine Hydroxylase-Positive Cells
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DOI：
10.1159/000495349
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发表时间：
2018-12
影响因子：
2.4
通讯作者：
M. Ebbinghaus;Z. Jenei-Lanzl;G. Segond von Banchet;H. Stangl;M. Gajda;R. Straub;H. Schaible
中科院分区：
文献类型：
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作者：
M. Ebbinghaus;Z. Jenei-Lanzl;G. Segond von Banchet;H. Stangl;M. Gajda;R. Straub;H. Schaible
目的：胶原诱导的关节炎中内源性酪氨酸羟化酶阳性细胞（TH+细胞）的出现与抗炎作用有关。在这里，我们研究了假定的抗炎和抗伤害性的影响，诱导骨髓干细胞衍生的TH+细胞（iTH+细胞）的小鼠抗原诱导的关节炎（AIA）的转移。方法：将骨髓源性干细胞诱导分化为iTH+细胞。将这些细胞转移到针对甲基化牛血清白蛋白（mBSA）免疫的小鼠中，然后通过将mBSA注射到一个膝关节中诱导AIA 2天。在AIA对照小鼠和iTH+处理的小鼠中，评估了AIA的严重程度、疼痛相关行为、体液和细胞反应以及巨噬细胞侵入背根神经节。结果如下：在AIA诱导之前静脉内转移iTH+细胞并没有引起AIA严重程度的持续抑制，但显著减少了炎症诱发的疼痛相关行为。用于转移的iTH+细胞表现出大量白细胞介素-4的产生。AIA对照小鼠和iTH+处理的AIA小鼠之间的主要差异是对应于M2表型的iNOS阴性、精氨酸1阳性巨噬细胞对背根神经节的大量侵袭。AIA对照小鼠和iTH+处理小鼠之间的其他细胞和体液免疫参数，如从刺激的淋巴细胞释放细胞因子的差异很小。结论：iTH+细胞的转移可能会导致关节炎引起的疼痛的持久减少，即使它没有改善炎症。M2巨噬细胞侵入背根神经节可能是其抗伤害感受的重要机制。
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.