人脐带间充质干细胞对新生鼠肺纤维化的防治作用

背景:间充质干细胞因具有自我增殖、多向分化潜能和旁分泌等功能,成为慢性肺部疾病细胞替代治疗的研究热点。目的:探讨人脐带间充质干细胞对新生大鼠肺纤维化的防治作用及对正常肺发育的影响。方法:将32只新生2dSD大鼠随机数字表法均分为PBS对照组、人脐带间充质干细胞组、博来霉素对照组,博来霉素+人脐带间充质干细胞组,后两组腹腔注射博来霉素建立肺纤维化模型,2个细胞组于第7天腹腔注射人脐带间充质干细胞。结果与结论:博来霉素对照组羟脯氨酸水平最高,肺纤维化最严重,与其他3组比较差异均有显著性意义(P<0.05);博来霉素干预的两组辐射状肺泡计数和肺组织匀浆中的转化生长因子β1mRNA表达均低于其他两组(P<0.05),但血管内皮生长因子mRNA表达升高(P<0.05),给予细胞治疗后,上述指标均有好转(P<0.05)。说明人脐带间充质干细胞能过旁分泌增加血管内皮生长因子mRNA表达,下调转化生长因子β1mRNA水平,对肺纤维化起保护作用。另外,正常鼠腹腔注射脐带间充质干细胞后辐射状肺泡计算无明显变化,证实其对新生鼠肺发育无明显影响。

Protective effects of human umbilical cord mesenchymal stem cells on lung fibrosis in newborn rats

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUMSCs) have become the hot spot of cytotherapy research about chronic lung disease, because of its capacity of self-prolifetion, differentiation and paracrine effect. OBJECTIVE: To study the protective effects of hUMSCs on lung fibrosis and normal lung growth in newborn rats. METHODS: Thirty-two 2-day-old newborn rats were randomly divided into four groups: PBS control group, hMSCs group, bleomycin group and bleomycin+hUMSCs group. Rats in the latter two groups were prepared into models of lung fibrosis by intraperitoneal injection of bleomycin, and two cell groups were injected with huMSCs at 7 days. RESULTS AND CONCLUSION: In the bleomycin group, the hydroxyproline content was the highest, and pulmonary fibrosis was the most severe compared with other three groups (P < 0.05). Compared with PBS control and hUMSCs groups, the radial alveolar count and transforming growth factor β1 expression in lung tissue homogenate were significantly lower, but the mRNA expression of vascular endothelial growth factor was significantly increased in the bleomycin and bleomycin+hUMSCs groups (both P < 0.05). After treatment, the above indices were significantly reversed (P < 0.05). It indicates that hUMSCs can increase the mRNA expression of vascular endothelial growth factor, reduce the level of transforming growth factor β1 mRNA and can produce a protective effect on bleomycin induced fibrosis. However, there is no obvious difference on hydroxyproline content after hUMSCs intraperitoneal injection, it confirms that hUMSCs have no effect on normal lung development.