本文選題：人源臍帶間充質(zhì)干細胞 + 胰島素樣生長因子-1��； 參考：《暨南大學(xué)》2017年博士論文

【摘要】：目的:研究人員目前已經(jīng)證實了人源臍帶間充質(zhì)干細胞(UC-MSCs)具有治療多種疾病的潛力。近年來,研究人員成功地將該細胞分化為神經(jīng)前體細胞(NPCs),為神經(jīng)疾病的治療提供了一種新的細胞來源。但是,在以后的臨床研究中,UC-MSCs向NPCs分化的方法仍需要進一步改進和完善。本研究旨在利用胰島素樣生長因子-1(IGF-1),優(yōu)化人源臍帶間充質(zhì)干細胞的神經(jīng)分化效率,為UC-MSCs在神經(jīng)系統(tǒng)疾病的臨床治療開發(fā)新的研究途徑。方法:通過逆轉(zhuǎn)錄病毒感染的方法建立胰島素樣生長因子-1(IGF-1)過度表達人源臍帶間充質(zhì)干細胞(UC-MSCs-IGF)模型,進而通過神經(jīng)誘導(dǎo)分化為神經(jīng)前體細胞。用RNA芯片,qPCR和western-blot分別檢測人源臍帶間充質(zhì)干細胞來源的神經(jīng)前體細胞的增殖和分化能力,以及相關(guān)通路機制。結(jié)果:與常規(guī)人源臍帶間充質(zhì)干細胞相比較,胰島素生長因子-1過表達的人源臍帶間充質(zhì)干細胞(UC-MSCs-IGF-1)分化而來的神經(jīng)前體細胞具有更強的增殖能力和更多的Pax6陽性以及Nestin陽性細胞。另外,UC-MSCs-IGF-1分化而來的神經(jīng)前體細胞在體外實驗中終末分化時可更高效率地分化為星形膠質(zhì)細胞。RNA芯片分析表明一些與神經(jīng)分化和神經(jīng)前體細胞增殖能力相關(guān)的基因在UC-MSCs-IGF-1中明顯上調(diào),并且該結(jié)論在qPCR和western-blot得到證實。最終,用IGF-1-siRNA轉(zhuǎn)染UC-MSCs-IGF-1,轉(zhuǎn)染后UC-MSCs-IGF-1衍生的神經(jīng)前體細胞增值能力和星形膠質(zhì)細胞分化能力減弱。結(jié)論:此研究表明胰島素樣生長因子-1可以提高人源臍帶間充質(zhì)干細胞的神經(jīng)分化能力,并且為增強人源臍帶間充質(zhì)干細胞衍生的神經(jīng)前體細胞向星形膠質(zhì)細胞分化提供了一項獨特的方法。
[Abstract]:Objective: human umbilical cord mesenchymal stem cells (UC-MSCs) have been demonstrated to have potential in the treatment of many diseases. In recent years, researchers have successfully differentiated the cells into neural precursor cells (NPCs), which provides a new source of cells for the treatment of neurological diseases. However, the differentiation of UC-MSCs into NPCs still needs to be further improved and improved in future clinical studies. The purpose of this study was to optimize the neural differentiation efficiency of human umbilical cord mesenchymal stem cells by using insulin-like growth factor-1 (IGF-1), and to develop a new approach for the clinical treatment of UC-MSCs in nervous system diseases. Methods: the UC-MSCs-IGF model of overexpression of human umbilical cord mesenchymal stem cells (UC-MSCs-IGF) was established by retrovirus infection and then differentiated into neural precursor cells. The proliferation and differentiation of neural progenitor cells derived from human umbilical cord mesenchymal stem cells were detected by RNA microarray qPCR and western-blot. Results: compared with normal human umbilical cord mesenchymal stem cells, UC-MSCs-IGF-1 derived human umbilical cord mesenchymal stem cells (UC-MSCs-IGF-1) derived from the overexpression of insulin growth factor 1 (IGF-1) have stronger proliferative ability, more Pax6 positive cells and more Nestin positive cells. In addition, UC-MSCs-IGF-1 differentiated neural progenitor cells could differentiate into astrocytes. RNA chip analysis showed that some genes related to neural differentiation and neural precursor cell proliferation were more efficiently differentiated during terminal differentiation in vitro. In UC-MSCs-IGF-1, it was significantly up-regulated, This conclusion is confirmed by qPCR and western-blot. Finally, after transfection of UC-MSCs-IGF-1 with IGF-1-siRNA, the proliferation and astrocyte differentiation ability of neural precursor cells derived from UC-MSCs-IGF-1 were decreased. Conclusion: this study suggests that insulin-like growth factor-1 can enhance the neural differentiation of human umbilical cord mesenchymal stem cells. It also provides a unique method for enhancing the differentiation of neural precursor cells derived from human umbilical cord mesenchymal stem cells into astrocytes.
【學(xué)位授予單位】：暨南大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R741

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