Gowhari Shabgah Arezoo, Shariati-Sarabi Zhaleh, Tavakkol-Afshari Jalil, Ghoryani Mohsen, Mohammadi Mojgan
Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Immunology Department, Mashhad University of Medical Sciences, Mashhad, Iran.
Int J Mol Cell Med. 2019 Summer;8(3):191-199. doi: 10.22088/IJMCM.BUMS.8.3.191.
The synovial- lining cells have been involved with rheumatoid arthritis (RA) through the secretion of various cytokines and chemokines. Increased levels of these cytokines and chemokines are seen first in the synovial and subsequently in the bloodstream of RA patients. The synovial and circulating levels of CXCL8, CXCL12, and CXCL13 are higher in the RA patients than in the healthy subjects, causing migration of immune cells to the joints, which is associated with increased joint destruction. We aimed to evaluate the effects of autologous mesenchymal stem cells intravenous administration on plasma levels of CXCL8, CXCL12 and CXCL13 at 1, 6, and 12 month follow-up periods in refractory RA patients. 13 patients with refractory RA received autologous mesenchymal stem cells (MSCs). The ELISA technique was used to evaluate the plasma level of these chemokines. CXCL8 levels were significantly decreased at month 6 after MSCs transplantation in comparison with pre-injection level, and the concentration of this chemokine was significantly increased at month 12 in comparison with the month 6 after injection (P <0.05). The levels of CXCL12 and CXCL13 were insignificantly decreased at months 1 and 6 after the MSCs transplantation. The interaction of MSCs after migration to the inflamed joints with CXCL8-producing cells could be one but not the only possible mechanism that reduces its production in the joints and subsequently in the plasma of RA patients. CXCL8 reduction as a consequence of MSCs application returned to pre-injection levels after 12 months. Therefore, increasing the dose of MSCs and replication of injections may maintain the potential anti-inflammatory effects of MSCs on the production of CXCL8 as an inflammatory mediator in patients with refractory RA.
滑膜衬里细胞通过分泌各种细胞因子和趋化因子参与类风湿性关节炎（RA）的发病过程。这些细胞因子和趋化因子水平的升高首先出现在RA患者的滑膜中，随后出现在其血液中。RA患者滑膜和循环中的CXCL8、CXCL12和CXCL13水平高于健康受试者，导致免疫细胞向关节迁移，这与关节破坏增加有关。我们旨在评估难治性RA患者在1个月、6个月和12个月随访期内静脉注射自体间充质干细胞对血浆中CXCL8、CXCL12和CXCL13水平的影响。13例难治性RA患者接受了自体间充质干细胞（MSCs）治疗。采用ELISA技术评估这些趋化因子的血浆水平。与注射前水平相比，MSCs移植后6个月时CXCL8水平显著降低，与注射后6个月相比，该趋化因子浓度在12个月时显著升高（P<0.05）。MSCs移植后1个月和6个月时，CXCL12和CXCL13水平无明显降低。MSCs迁移至炎症关节后与产生CXCL8的细胞相互作用可能是减少其在关节及随后在RA患者血浆中产生的一种机制，但不是唯一可能的机制。由于应用MSCs导致的CXCL8减少在12个月后恢复到注射前水平。因此，增加MSCs剂量和重复注射可能维持MSCs对难治性RA患者作为炎症介质的CXCL8产生的潜在抗炎作用。
