Department of Allergy and Clinical Immunology, Manisa City Hospital, Manisa, Turkey.
Department of Medical Biochemistry, Merkezefendi State Hospital, Manisa, Turkey.
Stem Cell Rev Rep. 2021 Jun;17(3):911-922. doi: 10.1007/s12015-020-10059-w. Epub 2020 Oct 22.
The etiopathogenesis of chronic spontaneous urticaria (CSU) is not fully elucidated, and almost 30-40% of patients are resistant to treatments; therefore, there is still a need for the development of new and effective treatments. This study aimed to develop experimental cellular therapy for CSU patients resistant to current treatment options. Autologous adipose tissue mesenchymal stem cells (MSC) were administered to 10 refractory CSU patients who were then followed up for six months. The efficacy of treatment was evaluated according to the weekly urticaria activity scores (UAS7) and drug use scores (DUS7). To observe the effect of treatment on immune cells, CD4 T cell subsets were analyzed by flow cytometry, and the serum IFN-γ, TNF-α, IL2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17a, IL-21, IL-22, TGF-β1, PGE2, IDO and anti-FcεRI levels were measured using the Luminex and ELISA methods. The values obtained were compared with 10 control refractory CSU patients and five healthy controls. We found that the T cell subsets and inflammatory molecules were not affected by MSC treatment during the follow-up period. In control patients, a significant decrease was detected only at the Th2 subset, TGF-β1, PGE2, IDO and anti-FcεRI levels on the 14th day of treatment. The UAS7 and DUS7 values of the MSC-treated patients significantly decreased during the follow-up period, but in control patients, a significant but temporary decrease was seen. According to our findings, unlike conventional treatment, MSC therapy resulted in longer and more effective recovery. Our data indicate that MSCs may be an alternative and effective approach for treatment-resistant CSU patients. Graphical Abstract.
慢性自发性荨麻疹(CSU)的发病机制尚未完全阐明,几乎 30-40%的患者对治疗有抵抗力;因此,仍然需要开发新的有效治疗方法。本研究旨在为对现有治疗方案有抵抗力的 CSU 患者开发实验性细胞治疗方法。将自体脂肪组织间充质干细胞(MSC)给予 10 例难治性 CSU 患者,然后进行六个月的随访。根据每周荨麻疹活动评分(UAS7)和药物使用评分(DUS7)评估治疗效果。为了观察治疗对免疫细胞的影响,通过流式细胞术分析 CD4 T 细胞亚群,并使用 Luminex 和 ELISA 方法测量血清 IFN-γ、TNF-α、IL2、IL-4、IL-5、IL-6、IL-10、IL-13、IL-17a、IL-21、IL-22、TGF-β1、PGE2、IDO 和抗-FcεRI 水平。将获得的值与 10 例对照难治性 CSU 患者和 5 例健康对照进行比较。我们发现,在随访期间,MSC 治疗不会影响 T 细胞亚群和炎症分子。在对照组患者中,仅在第 14 天治疗时观察到 Th2 亚群、TGF-β1、PGE2、IDO 和抗-FcεRI 水平显著下降。在 MSC 治疗患者中,UAS7 和 DUS7 值在随访期间显著下降,但在对照组患者中,仅暂时下降。根据我们的发现,与常规治疗不同,MSC 治疗导致更长和更有效的恢复。我们的数据表明,MSC 可能是治疗抵抗性 CSU 患者的一种替代和有效方法。图表摘要。