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人脐带间充质干细胞治疗通过抑制肥大细胞减轻间质性膀胱炎。

Human Umbilical Cord Mesenchymal Stem Cell Therapy Mitigates Interstitial Cystitis by Inhibiting Mast Cells.

机构信息

Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China (mainland).

出版信息

Med Sci Monit. 2021 Aug 6;27:e930001. doi: 10.12659/MSM.930001.

Abstract

BACKGROUND Interstitial cystitis (IC) is a recurrent and chronic inflammatory disease that compromises patients' quality of life. Effective treatments for IC are limited. This study aimed to evaluate the therapeutic potency of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) in an IC-induced rat model and investigate the potential molecular mechanism in a mast cell model (rat basophilic leukemia cells, RBL-2H3) in treating IC in a coculture system. MATERIAL AND METHODS The rat model of IC was induced by cyclophosphamide (CYP). Rats were randomly divided into 3 groups: sham, IC+PBS, and IC+MSC. In the coculture system, RBL-2H3 cells were sensitized overnight to Compound 48/80 (C48/80), cocultured with UC-MSCs for 3 days, and collected for subsequent experiments. RBL-2H3 cells were randomly divided into 3 groups: sham, C48, and UC-MSCs (C48+MSC). RESULTS The UC-MSCs marked by thymidine analog 5-ethynyl-2-deoxyuridine (EdU) were transplanted in the treatment group, and were densely distributed in the bladder. Accordingly, the conscious cystometry was measured and the bladder tissues were harvested. Compared with the sham group, the treated IC rats exhibited shorter bladder voiding intervals (307±35 vs 217±37 s; P<0.01), more integral epithelia, and less collagen fiber aggregation, infiltration and degranulation of mast cells, and inflammatory cytokines in the bladder tissue. In the coculture system, compared with the C48 group, the UC-MSC-treated RBL-2H3 cells had suppressed degranulation. CONCLUSIONS UC-MSCs treatment showed a promising therapeutic effect on treating IC in vivo and in vitro. UC-MSCs inhibit mast cell degranulation in IC and could be a potential therapeutic target to ameliorate inflammation in IC.

摘要

背景

间质性膀胱炎(IC)是一种反复发作的慢性炎症性疾病,会影响患者的生活质量。目前有效的治疗方法有限。本研究旨在评估人脐带间充质干细胞(UC-MSCs)在 IC 诱导的大鼠模型中的治疗效果,并在共培养系统中观察其在肥大细胞模型(大鼠嗜碱性白血病细胞,RBL-2H3)中治疗 IC 的潜在分子机制。

材料和方法

通过环磷酰胺(CYP)诱导大鼠 IC 模型。大鼠随机分为 3 组:假手术组、IC+PBS 组和 IC+MSC 组。在共培养系统中,RBL-2H3 细胞经 Compound 48/80(C48/80)敏化过夜,与 UC-MSCs 共培养 3 天,然后收集进行后续实验。RBL-2H3 细胞随机分为 3 组:假手术组、C48 组和 UC-MSCs 组(C48+MSC 组)。

结果

用胸腺嘧啶类似物 5-乙炔基-2-脱氧尿苷(EdU)标记的 UC-MSCs 移植到治疗组中,在膀胱中密集分布。因此,进行清醒膀胱测压并采集膀胱组织。与假手术组相比,治疗后的 IC 大鼠膀胱排空间隔明显缩短(307±35 比 217±37 s;P<0.01),膀胱上皮完整,胶原纤维聚集、肥大细胞浸润和脱颗粒以及膀胱组织中炎症细胞因子减少。在共培养系统中,与 C48 组相比,UC-MSC 处理的 RBL-2H3 细胞脱颗粒受到抑制。

结论

UC-MSCs 治疗在体内和体外均显示出对 IC 有较好的治疗效果。UC-MSCs 抑制 IC 中肥大细胞脱颗粒,可能是改善 IC 炎症的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ab/8353995/53910f023a73/medscimonit-27-e930001-g001.jpg

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