Li Ning, Zhang Yichi, Nepal Narayan, Li Guoqing, Yang Ningning, Chen Haoyuan, Lin Qiuchi, Ji Xuechun, Zhang Sijia, Jin Shizhu
Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
Stem Cell Res Ther. 2021 Jan 7;12(1):30. doi: 10.1186/s13287-020-02098-4.
Ulcerative colitis (UC) is a chronic and recurrent disease without satisfactory treatment strategies. Dental pulp stem cell (DPSC) transplantation has been proposed as a potential therapy for UC. This study aimed to investigate the therapeutic effects of the rat hepatocyte growth factor (HGF) gene transduced into DPSCs for UC.
The therapeutic effects of HGF-DPSCs transplanted intravenously into a rat model of UC induced by 5% dextran sulphate sodium (DSS) were compared with the other treatment groups (LV-HGF group, DPSCs group and GFP-DPSCs group). Immunofluorescence and immunohistochemistry were used to observe the localization and proliferation of HGF-DPSCs at the site of colon injury. The expression levels of inflammatory factors were detected by real-time quantitative PCR (RT-PCR) and western blotting. The oxidative stress markers were detected by ELISA. DAI scores and body weight changes were used to macroscopically evaluate the treatment of rats in each group.
Immunofluorescence and immunohistochemistry assays showed that HGF-DPSCs homed to colon injury sites and colocalized with intestinal stem cell (ISC) markers (Bmi1, Musashi1 and Sox9) and significantly promoted protein expression (Bmi1, Musashi1, Sox9 and PCNA). Anti-inflammatory cytokine (TGF-β and IL-10) expression was the highest in the HGF-DPSCs group compared with the other treatment groups, while the expression of pro-inflammatory cytokines (TNF-α and INF-γ) was the lowest. Additionally, the oxidative stress response results showed that malondialdehyde (MDA) and myeloperoxidase (MPO) expression decreased while superoxide dismutase (SOD) expression increased, especially in the HGF-DPSCs group. The DAI scores showed a downward trend with time in the five treatment groups, whereas body weight increased, and the changes were most prominent in the HGF-DPSCs group.
The study indicated that HGF-DPSCs can alleviate injuries to the intestinal mucosa by transdifferentiating into ISC-like cells, promoting ISC-like cell proliferation, suppressing inflammatory responses and reducing oxidative stress damage, which provides new ideas for the clinical treatment of UC.
溃疡性结肠炎（UC）是一种慢性复发性疾病，目前尚无令人满意的治疗策略。牙髓干细胞（DPSC）移植已被提议作为UC的一种潜在治疗方法。本研究旨在探讨转导大鼠肝细胞生长因子（HGF）基因的DPSCs对UC的治疗效果。
将静脉注射HGF-DPSCs至5%葡聚糖硫酸钠（DSS）诱导的UC大鼠模型中的治疗效果与其他治疗组（LV-HGF组、DPSCs组和GFP-DPSCs组）进行比较。采用免疫荧光和免疫组织化学方法观察HGF-DPSCs在结肠损伤部位的定位和增殖情况。通过实时定量PCR（RT-PCR）和蛋白质印迹法检测炎症因子的表达水平。采用酶联免疫吸附测定（ELISA）检测氧化应激标志物。采用疾病活动指数（DAI）评分和体重变化对各组大鼠的治疗情况进行宏观评估。
免疫荧光和免疫组织化学分析显示，HGF-DPSCs归巢至结肠损伤部位，并与肠干细胞（ISC）标志物（Bmi1、Musashi1和Sox9）共定位，且显著促进蛋白表达（Bmi1、Musashi1、Sox9和增殖细胞核抗原（PCNA））。与其他治疗组相比，HGF-DPSCs组抗炎细胞因子（转化生长因子-β（TGF-β）和白细胞介素-10（IL-10））表达最高，而促炎细胞因子（肿瘤坏死因子-α（TNF-α）和干扰素-γ（INF-γ））表达最低。此外，氧化应激反应结果显示，丙二醛（MDA）和髓过氧化物酶（MPO）表达降低，而超氧化物歧化酶（SOD）表达增加，尤其是在HGF-DPSCs组。五个治疗组的DAI评分随时间呈下降趋势，而体重增加，且在HGF-DPSCs组变化最为显著。
该研究表明，HGF-DPSCs可通过向ISC样细胞转分化、促进ISC样细胞增殖、抑制炎症反应和减少氧化应激损伤来减轻肠黏膜损伤，为UC的临床治疗提供了新思路。
