誘導(dǎo)多能干細(xì)胞對(duì)骨關(guān)節(jié)炎軟骨損傷的修復(fù)作用
本文選題:骨關(guān)節(jié)炎 + 誘導(dǎo)多功能干細(xì)胞; 參考:《中國(guó)組織工程研究》2017年33期
【摘要】:背景:基于干細(xì)胞的細(xì)胞治療對(duì)于骨關(guān)節(jié)炎修復(fù)有重要的應(yīng)用前景,其中誘導(dǎo)多能干細(xì)胞(induced pluripotent stem cell,i PS細(xì)胞)具有較強(qiáng)的增殖和分化潛能,且避免了胚胎干細(xì)胞的倫理學(xué)問題,目前被認(rèn)為是細(xì)胞治療中最有前景的種子細(xì)胞之一。目的:擬探索一種i PS細(xì)胞向軟骨細(xì)胞分化的有效方法,并研究i PS細(xì)胞來(lái)源軟骨細(xì)胞對(duì)骨關(guān)節(jié)炎的修復(fù)作用。方法:運(yùn)用三步法將人i PS細(xì)胞誘導(dǎo)分化成軟骨樣細(xì)胞,并檢測(cè)軟骨細(xì)胞特異性基因和蛋白的表達(dá)。然后將分化后的i PS細(xì)胞移植到谷氨酸鈉碘乙酸誘導(dǎo)的骨關(guān)節(jié)炎大鼠模型中。移植實(shí)驗(yàn)分為4組:對(duì)照組注射生理鹽水,造模組注射谷氨酸鈉碘乙酸,i PS細(xì)胞移植組注射谷氨酸鈉碘乙酸后移植i PS細(xì)胞,分化后i PS細(xì)胞移植組注射谷氨酸鈉碘乙酸后移植軟骨分化后的i PS細(xì)胞。移植15周后micro-CT行斷層掃描,并對(duì)移植后的關(guān)節(jié)進(jìn)行組織學(xué)分析。結(jié)果與結(jié)論:(1)與未分化的i PS細(xì)胞相比,經(jīng)過6 d的擬胚體形成和2周的細(xì)胞分化,軟骨細(xì)胞特異性基因和蛋白(Col2A1,GAG和Sox9)的表達(dá)量都明顯上升;(2)細(xì)胞移植15周后,未觀察到免疫反應(yīng)的發(fā)生,micro-CT顯示移植細(xì)胞后軟骨下骨的完整性明顯得到改善,組織學(xué)分析也表明移植細(xì)胞后能產(chǎn)生關(guān)節(jié)軟骨基質(zhì)。i PS細(xì)胞來(lái)源軟骨細(xì)胞的修復(fù)效果明顯好于i PS細(xì)胞;(3)結(jié)果表明,i PS細(xì)胞來(lái)源軟骨細(xì)胞移植可促進(jìn)骨關(guān)節(jié)炎大鼠軟骨再生,改善關(guān)節(jié)功能。
[Abstract]:Background: Stem cell based cell therapy has an important application prospect for osteoarthritis repair, among which induced pluripotent stem cell PS cells have strong proliferation and differentiation potential, and avoid the ethical problems of embryonic stem cells. Currently, it is considered to be one of the most promising seed cells in cell therapy. Aim: to explore an effective method for the differentiation of iPS cells into chondrocytes and to study the repair effect of iPS derived chondrocytes on osteoarthritis. Methods: human I PS cells were induced to differentiate into chondroid cells by three steps method, and the expression of specific genes and proteins in chondrocytes was detected. Then the differentiated iPS cells were transplanted into the rat model of osteoarthritis induced by sodium glutamate iodoacetic acid. The transplantation experiment was divided into four groups: control group was injected with normal saline, model group was injected with sodium glutamate iodoacetic acid and I PS cells were injected with sodium glutamate iodoacetic acid, and I PS cells were transplanted after injection. I PS cells were transplanted into differentiated cartilage after injection of sodium glutamate and iodoacetic acid. Micro-CT scanning was performed 15 weeks after transplantation and histological analysis of the transplanted joints was performed. Results after 6 days of embryoid formation and 2 weeks of cell differentiation, the expression of specific gene and protein of chondrocyte (Col2A1GG and Sox9) in chondrocytes increased significantly 15 weeks after transplantation compared with undifferentiated iPS cells. No immunoreaction was observed. Micro-CT showed that the integrity of subchondral bone was significantly improved after transplantation. Histological analysis also showed that the repair effect of chondrocytes derived from articular cartilage matrix. IPS cells after transplantation was significantly better than that from iPS cells. The results showed that the transplantation of chondrocytes derived from iPS cells could promote cartilage regeneration in osteoarthritis rats. Improve joint function.
【作者單位】: 深圳大學(xué)醫(yī)學(xué)部深圳抗衰老與再生醫(yī)學(xué)重點(diǎn)實(shí)驗(yàn)室;孝感市婦幼保健院脊柱外科;
【基金】:國(guó)家自然科學(xué)基金(81301597) 深圳新興戰(zhàn)略產(chǎn)業(yè)發(fā)展專項(xiàng)資金(JCYJ20130326110154156/JCYJ2015052509 2940984/JCYJ20160422090807181)~~
【分類號(hào)】:R684.3
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