| 何继晨,严君逸,程琢玉,等.诱导多能干细胞来源间充质干细胞对大鼠骨关节炎的治疗作用[J].安徽医药,2019,23(8):1496-1500. |
| 诱导多能干细胞来源间充质干细胞对大鼠骨关节炎的治疗作用 |
| Therapeutic roles of induced pluripotent stem cell-derived mesenchymal stem cells on experimental model of osteoarthritis |
| 投稿时间：2019-01-17 |
| DOI： |
| 中文关键词: 骨关节炎 脐血干细胞移植 注射,关节内 诱导多能干细胞 间质干细胞 软骨损伤 大鼠 |
| 英文关键词: Osteoarthritis Cord blood stem cell transplantation Injections,intra-articular Induced pluripotent stem cells Mesenchymal stem cells Cartilage injury Rats |
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| 中文摘要: |
| 目的 研究诱导多能干细胞来源间充质干细胞(iPSC-MSCs)对大鼠骨关节炎(OA)的治疗作用。方法 采用Hulth法建立大鼠OA模型,编号后运用Excel表格随机分组功能将其分为模型组、iPSC-MSCs组、人脐带来源间充质干细胞(hUC-MSCs)组、玻璃酸钠(HA)阳性对照组,另设假手术组作为对照,每组10只。除HA组动物多次给药(每周1次,共给药5次)外,其它各组均单次给药,每次每只动物在术侧关节腔注射50 μL药物iPSC-MSCs和hUC-MSCs,假手术组和模型组同法给予生理盐水。给药5周后处死动物,观察iPSC-MSCs对关节直径差值、关节腔结构及评分、关节面评分、病理学评分等指标的影响；检测膝关节基质金属蛋白酶(MMP)-13、Ⅱ型胶原(CollagenⅡ)及解聚蛋白样金属蛋白酶(ADAMTS)-5表达情况。结果 iPSC-MSCs和hUC-MSCs给药均可显著降低膝关节面Pelletier评分、关节直径和病理Mankin评分,改善关节腔结构,降低X线评分和关节肿胀,且iPSC-MSCs较hUC-MSCs给药在降低Pelletier评分[(1.22±0.67)比(2.00±0.71),P=0.021]方面差异有统计学意义；相比于模型组,iPSC-MSCs关节腔注射给药可显著增加软骨层CollagenⅡ表达[(35.87±8.52)比(69.90±7.65),P＜0.01],降低MMP-13[(59.25±5.56)比(33.75±5.85),P＜0.01]和ADAMTS-5[(52.25±10.47)比(22.25±6.13),P＜0.01]表达水平,且与hUC-MSCs给药差异有统计学意义,iPSC-MSCs组与hUC-MSCs组CollagenⅡ、MMP-13、ADAMTS-5值分别为[(69.90±7.65)比(61.00±5.52),P=0.010]、[(33.75±5.85)比(43.25±6.02),P=0.028]、[(22.25±6.13)比(36.50±4.65),P=0.011]。结论 关节腔注射iPSC-MSCs可显著改善OA大鼠关节病理,具有明显的软骨保护作用。 |
| 英文摘要: |
| Objective To elucidate the protective effects of induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) on osteoarthritis (OA) in rats.Methods The OA model was established by Hulth method and 50 rats were randomized into sham group (control group),model group,iPSC-MSCs group,human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) group,and hyaluronic acid (HA) positive control group,and each group with 10 rats.Rats in the HA group were given multiple dosing (once a week,a total of 5 times),rats in sham and model groups were dealt with 50 μL saline,all the other rats were injected with 50 μL drugs in the joint of the surgery side.At the end of 5th week,rats were sacrificed by cervical dislocation.The joint diameter difference,joint cavity structure and score,articular surface score,pathological score and other indicators were observed.The expression of matrix metalloproteinase (MMP)-13,type Ⅱ collagen (Collagen Ⅱ) and depolymerized protein-like metalloproteinase (ADAMTS)-5 were detected.Results Administration of iPSC-MSCs and hUC-MSCs markedly reduced the knee joint Pelletier score,joint diameter and pathological Mankin score,improved joint cavity structure,and decreased X-ray score and joint swelling.The Pelletier score in hUC-MSCs group and iPSC-MSCs group has statistical difference [(2.00±0.71) vs.(1.22±0.67),P=0.021].Compared with model group,administration with iPSC-MSCs significantly increased the expression of Collagen Ⅱ in the cartilage layer [(35.87±8.52) vs.(69.90±7.65),P<0.01],inhibited the expression of MMP-13 [(59.25±5.56) vs.(33.75±5.85),P<0.01] and ADAMTS-5 [(52.25±10.47) vs.(22.25±6.13),P<0.01].Compared with hUC-MSCs group,administration with iPSC-MSCs was more effective in increasing CollagenⅡlevel [(69.90±7.65) vs.(61.00±5.52),P=0.010],and reducing the expression of MMP-13 [(33.75±5.85) vs.(43.25±6.02),P=0.028] and ADAMTS-5 [(22.25±6.13) vs.(36.50±4.65),P=0.011].ConclusioniPSC-MSCs could improve the joint pathology of OA rats and may exert the obvious protective effects on cartilage. |
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