本文選題：GAP-43　切入點：骨髓間充質(zhì)干細胞　出處：《吉林大學(xué)》2009年博士論文

【摘要】： 近年來隨著干細胞領(lǐng)域研究的不斷深入,為探索神經(jīng)細胞變性或損傷性疾病的治療提供了新的思路。骨髓間充質(zhì)干細胞(BMSCs)具有多向分化潛能,目前已成為成體干細胞領(lǐng)域研究的熱點。生長相關(guān)蛋白-43(GAP-43)被認為是神經(jīng)元發(fā)育和再生的一個內(nèi)在決定因子,與神經(jīng)發(fā)育、再生密切相關(guān),因此明確GAP-43在BMSCs向神經(jīng)樣細胞分化過程中的作用對于洞悉干細胞的定向分化機制具有重要意義。 本研究分別應(yīng)用化學(xué)誘導(dǎo)劑、生長因子及視網(wǎng)膜條件分化液誘導(dǎo)大鼠BMSCs定向分化為神經(jīng)樣細胞,在此過程中均檢測到GAP-43持續(xù)性表達,提示其參與了分化過程并可能發(fā)揮重要作用。此外,應(yīng)用基因克隆技術(shù)將GAP-43基因克隆并構(gòu)建到pcDNA3.1(+)載體,轉(zhuǎn)染BMSCs后細胞表達GAP-43,并且向神經(jīng)樣細胞分化能力得到提高,在視網(wǎng)膜條件分化液誘導(dǎo)環(huán)境下此種能力提高更加明顯。同時,利用RNA干擾技術(shù)構(gòu)建出GAP-43-shRNA表達載體,轉(zhuǎn)染BMSCs后在誘導(dǎo)條件下可特異性抑制GAP-43基因的表達,基因沉默后BMSCs向神經(jīng)樣細胞分化能力受到明顯抑制。 通過上述研究證明GAP-43為體外培養(yǎng)的BMSCs向神經(jīng)樣細胞分化過程中發(fā)揮重要作用的基因之一,表達GAP-43基因?qū)⒋龠MBMSCs向神經(jīng)樣細胞分化,抑制該基因表達后細胞分化能力減弱。研究結(jié)果對于進一步探索干細胞定向分化機理和可應(yīng)用于臨床的基因治療方法奠定了理論基礎(chǔ)。
[Abstract]:In recent years , with the deepening of research in the field of stem cells , it provides a new idea for exploring the treatment of neural cell degeneration or injury diseases . Bone marrow mesenchymal stem cells ( MSCs ) have the potential to differentiate into adult stem cells . The growth - related protein - 43 ( GAP - 43 ) is considered to be an intrinsic determinant of neuronal development and regeneration , which is closely related to neurodevelopment and regeneration . It is therefore clear that GAP - 43 plays an important role in the differentiation of neural - like cells .


In addition , GAP - 43 gene was cloned and constructed into pcDNA3.1 ( + ) vector . GAP - 43 gene was cloned and transfected into pcDNA3.1 ( + ) vector .


It is proved that GAP - 43 gene plays an important role in the differentiation of neural - like cells in vitro . The expression of GAP - 43 gene will promote the differentiation of bone marrow cells into neural - like cells , and decrease the cell differentiation ability after the gene expression . The results of this study have laid a theoretical foundation for further exploring the mechanism of stem cell differentiation and the application of gene therapy in clinic .

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2009
【分類號】：R329

【參考文獻】

相關(guān)期刊論文 前10條

1 單志新;林秋雄;李曉紅;鄧春玉;周志凌;黃薇;黃曉忠;余細勇;;腺病毒表達載體對骨髓間充質(zhì)干細胞分化能力的影響[J];南方醫(yī)科大學(xué)學(xué)報;2008年07期

2 劉金保,董曉先,董燕湘,何慧華,董偉華,梁仲培,肖慶忠;當(dāng)歸誘導(dǎo)骨髓間充質(zhì)干細胞分化為神經(jīng)元樣細胞[J];廣東醫(yī)學(xué);2003年05期

3 孫吉平,賈延R，

本文編號：1688111