發(fā)布時(shí)間：2018-05-21 03:09

  本文選題：間充質(zhì)干細(xì)胞 + miRNA�。� 參考：《第四軍醫(yī)大學(xué)》2016年碩士論文

【摘要】：【背景】近年來,由病毒、酒精、毒物或代謝等因素引起的肝臟衰竭呈逐年上升趨勢(shì)。特別是急性、亞急性及慢加急性肝功能衰竭,由于病因多,并發(fā)癥多和重要器官損傷多等特點(diǎn),成為高發(fā)病率、高死亡率和治療非常棘手的疾病。肝移植是治療肝衰竭最有效的手段,但供肝的嚴(yán)重缺乏、治療費(fèi)用昂貴及移植后的免疫排斥反應(yīng)等限制了它的廣泛應(yīng)用。人工肝支持系統(tǒng)可部分地清除體內(nèi)的毒性代謝產(chǎn)物,給患者自身肝臟再生創(chuàng)造條件。但由于其沒有肝臟的合成及代謝等功能,其治療療效有限。因此,急需開發(fā)具有一定肝臟功能的生物型人工肝支持系統(tǒng)。近年來,生物型人工肝支持系統(tǒng)逐漸成為治療急性肝衰竭最有效和最具潛力的治療方式。生物型人工肝支持系統(tǒng)主要由細(xì)胞成分,生物反應(yīng)器及輔助器材組成,其中細(xì)胞成分是生物型人工肝的核心問題。目前,種子細(xì)胞來源受到很多方面的限制,諸如自體肝細(xì)胞體外培養(yǎng)、增殖和保存技術(shù)有限,異種來源肝細(xì)胞存在免疫排斥效應(yīng)等。這些因素限制了生物型人工肝支持系統(tǒng)應(yīng)用于肝功能衰竭的治療。因此,我們需要尋找有功能的人源肝細(xì)胞,并可大規(guī)模生產(chǎn)。而近年來干細(xì)胞的發(fā)展為解決肝細(xì)胞來源提供了新的思路。我們前期研究通過對(duì)間充質(zhì)干細(xì)胞誘導(dǎo)分化得到的肝細(xì)胞樣細(xì)胞HLC與間充質(zhì)干細(xì)胞的micro RNA表達(dá)水平進(jìn)行芯片分析,以及RT-PCR驗(yàn)證比對(duì)等獲得一組表達(dá)量顯著上調(diào)的micro RNA組合:mi R-148a,mi R-424,mi R-1290,mi R-542-5p,mi R-1246和mi R-30a。在此基礎(chǔ)上,我們加入了肝臟特異性的mi R-122,作為一組micro RNA即7個(gè)mi RNA組合轉(zhuǎn)染進(jìn)人臍帶間充質(zhì)干細(xì)胞內(nèi),成功實(shí)現(xiàn)了干細(xì)胞轉(zhuǎn)分化為肝細(xì)胞樣細(xì)胞(hepatocyte-like cells 7,HLC-7),并進(jìn)行了一系列肝細(xì)胞樣細(xì)胞的功能驗(yàn)證。我們證實(shí)這組由mi RNA組合誘導(dǎo)得到的細(xì)胞不僅表達(dá)肝特異基因,還具有LDL攝取,糖原沉積,尿素合成等一系列肝細(xì)胞功能。進(jìn)一步,我們通過每組減少一種mi RNA獲得不同組合方式的方法繼續(xù)篩選對(duì)于人臍帶間充質(zhì)干細(xì)胞轉(zhuǎn)分化為肝細(xì)胞樣細(xì)胞的關(guān)鍵mi RNA或者組合。我們通過刪減mi R-30a和mi R-1290后的5種mi RNA(mi R-122,mi R-148a,mi R-424,mi R-542-5p和mi R-1246)轉(zhuǎn)染進(jìn)臍帶MSC中,成功將其誘導(dǎo)分化為肝細(xì)胞樣細(xì)胞(HLC-5),能夠表達(dá)肝臟特異性基因ALB,AFP,HNF4A和TF等,PAS染色和LDL攝取試驗(yàn)均為陽性,證實(shí)了誘導(dǎo)分化的成功。本研究將繼續(xù)采用n-1方法進(jìn)一步刪減mi RNA組合,并驗(yàn)證其體外的肝細(xì)胞功能。運(yùn)用四氯化碳(Carbon tetrachloride,CCl4)建立裸鼠肝損傷和急性肝衰竭模型,并對(duì)肝損傷小鼠進(jìn)行HLC移植治療,觀察對(duì)動(dòng)物模型的修復(fù)作用�！灸康摹�1.明確mi RNA介導(dǎo)間充質(zhì)干細(xì)胞轉(zhuǎn)分化為肝細(xì)胞樣細(xì)胞的最優(yōu)組合;2.闡明HLCs在裸鼠肝損傷和肝衰竭中的修復(fù)作用�！痉椒ā�1.貼壁培養(yǎng)MSC,倒置顯微鏡觀察細(xì)胞形態(tài),流式細(xì)胞儀檢測(cè)表面標(biāo)志,進(jìn)行成脂和成骨誘導(dǎo)分化,明確MSC的純度和分化能力。2.篩檢mi RNA組合:驗(yàn)證5種mi RNA(mi R-122,148a,424,542-5p和1246)的轉(zhuǎn)染效率以及誘導(dǎo)間充質(zhì)干細(xì)胞轉(zhuǎn)分化為肝細(xì)胞樣細(xì)胞的能力。在此基礎(chǔ)上,逐漸減少mi RNA的個(gè)數(shù),觀察轉(zhuǎn)染后的效應(yīng):主要通過RT-PCR檢測(cè)肝特異性基因表達(dá)水平,LDL攝取實(shí)驗(yàn)、ICG攝取實(shí)驗(yàn)、PAS糖原染色和尿素氮合成等試驗(yàn)檢測(cè)HLC的肝細(xì)胞特異性功能。3.CCl4誘導(dǎo)裸鼠肝損傷,并隨機(jī)分為生理鹽水陰性對(duì)照組,HLC-7陽性對(duì)照和最優(yōu)組合誘導(dǎo)的HLC-N組,將生理鹽水和誘導(dǎo)細(xì)胞經(jīng)裸鼠尾靜脈移植(細(xì)胞數(shù)量1x106/只)。通過血清學(xué)檢測(cè)AST、ALT、ALB水平,HE染色和天狼星紅染色觀察造模損傷程度和細(xì)胞移植后的修復(fù)情況。4.高濃度CCl4誘導(dǎo)裸鼠急性肝衰竭,隨機(jī)分為生理鹽水陰性對(duì)照組,HLC-7陽性對(duì)照和最優(yōu)組合誘導(dǎo)的HLC-N組,并經(jīng)裸鼠尾靜脈進(jìn)行移植。一周內(nèi)觀察裸鼠的生存情況。【結(jié)果】1.貼壁培養(yǎng)的MSC呈類成纖維樣的梭形形態(tài),流式細(xì)胞儀檢測(cè)MSC表達(dá)99.8%的標(biāo)志分子CD105,而造血干細(xì)胞標(biāo)志CD34以及內(nèi)皮細(xì)胞標(biāo)志CD31陽性率僅為0.2%,0.2%,表明MSC細(xì)胞純度較高。另外,茜素紅和油紅染色結(jié)果顯示MSC可以在誘導(dǎo)液作用下分化為骨細(xì)胞和脂肪細(xì)胞,具備多向分化的潛能。2.5種mi RNA轉(zhuǎn)染后的結(jié)果顯示:在轉(zhuǎn)染7天后,5種mi RNA均在轉(zhuǎn)染細(xì)胞中成功過表達(dá);與NC組相比,HLC-5的肝特異性基因ALB,HNF4A,AFP等表達(dá)水平顯著升高,與HLC-7類似;而不表達(dá)其他非特異的PDX1,Ep CAM和CK7。肝特異性功能檢測(cè)結(jié)果顯示:LDL和ICG攝取實(shí)驗(yàn)表明大部分的HLC-5可以攝取LDL,約40%可以攝取ICG;PAS染色結(jié)果提示大約60%的HLC-5都可以合成糖原;尿素合成實(shí)驗(yàn)表明HLC-5具備合成尿素的能力,與對(duì)照組相比,具有統(tǒng)計(jì)學(xué)意義。3.4種mi RNA轉(zhuǎn)染后的結(jié)果顯示:轉(zhuǎn)染7天后,各組的細(xì)胞形態(tài)并無明顯改變;RT-PCR的結(jié)果顯示各組間ALB,HNF4A,AFP,CYP3A4和TF的m RNA水平與對(duì)照組相比并無明顯差異;LDL攝取實(shí)驗(yàn)也表明4種mi RNA誘導(dǎo)的細(xì)胞不能成功攝取LDL。4.急性肝損傷模型結(jié)果顯示:CCl4處理后血清ALB明顯下降,AST和ALT升高,HE染色可見肝臟結(jié)構(gòu)破壞和炎細(xì)胞浸潤(rùn),提示急性肝損傷模型建立成功。與生理鹽水處理組相比,HLC-5和HLC-7移植后白蛋白水平升高,轉(zhuǎn)氨酶水平下降,血清結(jié)果明顯改善;HE染色提示肝臟組織結(jié)構(gòu)改善,炎癥減輕。5.急性肝衰竭模型結(jié)果表明:高濃度CCl4處理1天后,HE染色結(jié)果顯示肝臟組織結(jié)構(gòu)受損嚴(yán)重,炎性細(xì)胞浸潤(rùn)。觀察一周內(nèi)的生存情況發(fā)現(xiàn),與生理鹽水對(duì)照組相比,HLC-5和HLC-7移植后可顯著改善裸鼠的生存時(shí)間。并且HLC-5和HLC-7兩組間并無明顯差異,說明在體內(nèi)HLC-5具有與HLC-7相似的功能。【結(jié)論】本研究表明,5種mi RNA(mi R-122,148a,424,542-5p和1246)是誘導(dǎo)臍帶間充質(zhì)干細(xì)胞轉(zhuǎn)分化為肝細(xì)胞樣細(xì)胞的最優(yōu)組合。誘導(dǎo)得到的HLC-5不僅在體外具備肝細(xì)胞的功能,在動(dòng)物模型體內(nèi)也可發(fā)揮與HLC-7相似的損傷修復(fù)功能,并可顯著改善肝衰竭裸鼠的生存情況。這為肝細(xì)胞樣細(xì)胞在生物性人工肝的應(yīng)用提供了實(shí)驗(yàn)基礎(chǔ)。而mi RNA調(diào)控轉(zhuǎn)分化的具體機(jī)制和HLC-5的細(xì)胞特點(diǎn)尚需要進(jìn)一步探索。
[Abstract]:[background] in recent years, liver failure caused by virus, alcohol, poison or metabolism has been increasing year by year. Especially acute, subacute and slow and acute liver failure, due to many causes, many complications and many important organ damage, it has become a high incidence, high mortality and very difficult treatment. Liver transplantation is a serious disease. The most effective means for the treatment of liver failure, but the severe deficiency of the donor liver, the expensive treatment and the immune rejection after the transplantation limit its wide application. The artificial liver support system can partially remove the toxic metabolites in the body and create conditions for the patient's own liver regeneration. However, it has no function of liver synthesis and metabolism. In recent years, biological artificial liver support system has gradually become the most effective and potential treatment for acute liver failure. Biological artificial liver support system is mainly composed of cell components, bioreactors and auxiliary equipment groups. The cell composition is the core problem of the biotype artificial liver. At present, the source of seed cells is limited by many aspects, such as the culture of autologous liver cells in vitro, the limited proliferation and preservation techniques, and the immune rejection of xenogenic liver cells. These factors restrict the application of biological artificial liver support system to liver failure. Therefore, we need to find functional human derived hepatocytes and can be produced on a large scale. In recent years, the development of stem cells provides a new way of thinking for the solution of hepatocyte origin. We have studied the level of micro RNA expression of HLC and mesenchymal stem cells derived from mesenchymal stem cells. Chip analysis, and RT-PCR validation is a micro RNA combination that is significantly up - up of a set of expressions than peer to peer: Mi R-148a, MI R-424, MI R-1290, MI R-542-5p. The stem cells were transformed into hepatocyte like cells (hepatocyte-like cells 7, HLC-7), and the function of a series of hepatocyte like cells was verified. We confirmed that this group of cells induced by Mi RNA combination not only expressed liver specific genes, but also had a series of hepatocyte functions, such as LDL uptake, glycogen deposition, urea synthesis, and so on. We continue screening the key mi RNA or combination of human umbilical cord mesenchymal stem cells transdifferentiated into hepatocyte like cells by reducing one kind of MI RNA in each group. We transfect the 5 mi RNA of MI R-30a and MI R-12 90 (MI R-122) into umbilical cord It is successfully induced to differentiate into hepatocyte like cells (HLC-5), which can express liver specific genes ALB, AFP, HNF4A and TF. Both PAS staining and LDL uptake test are positive, which confirm the success of induced differentiation. This study will continue to use n-1 method to further reduce the MI RNA combination and verify the function of liver cells in vitro. Using carbon tetrachloride in vitro. (Carbon tetrachloride, CCl4) to establish a model of liver injury and acute liver failure in nude mice, and to treat the mice with liver injury by HLC transplantation and observe the repair effect of the animal model. [Objective] 1. to clarify the optimal combination of MI RNA mediated mesenchymal stem cells to turn into hepatocyte like cells; and 2. clarify HLCs in nude mice liver injury and liver failure. Repair effect. [Methods] 1. adherent culture MSC, inverted microscope to observe cell morphology, flow cytometry to detect surface markers, lipid and osteogenesis induced differentiation, clear MSC purity and differentiation ability.2. screening mi RNA combination: verify the transfection efficiency of 5 mi RNA (MI R-122148a, 424542-5p and 1246) and induce mesenchymal stem cells to transfer. The ability to differentiate into hepatocyte like cells. On this basis, the number of MI RNA was gradually reduced and the effect after transfection was observed: the detection of liver specific gene expression by RT-PCR, LDL uptake experiment, ICG uptake experiment, PAS glycogen staining and urea nitrogen synthesis test to detect the liver cell specific function.3.CCl4 of HLC to induce liver injury in nude mice And randomly divided into the normal saline negative control group, the HLC-7 positive control and the optimal combination induced HLC-N group, the physiological saline and the induced cells were transplanted in the tail vein of nude mice (the number of cells 1x106/ only). By serological detection of AST, ALT, ALB level, HE staining and Sirius red staining, the damage degree of the model and the restoration of the cells after the cell transplantation were observed. The high concentration of CCl4 induced acute liver failure in nude mice, randomly divided into the normal saline negative control group, the HLC-7 positive control and the optimal combination induced HLC-N group, and transplantable by the tail vein of nude mice. In a week, the survival of nude mice was observed. [results] the MSC of 1. adherent culture was like the spindle shape of the fibrinolytic type, and the flow cytometry was used to detect the MSC expression. 99.8% of the marker molecule CD105, and the hematopoietic stem cell marker CD34 and the endothelial cell marker CD31 positive rate is only 0.2%, 0.2%, indicating that the MSC cell purity is high. In addition, alizarin red and oil red staining results show that MSC can differentiate into bone and fat cells under the action of inducer, with the potential of multidirectional differentiation potential.2.5 species after MI RNA transfected. The results showed that 7 days after transfection, 5 kinds of MI RNA were overexpressed in transfected cells. Compared with group NC, the expression level of HLC-5 specific gene ALB, HNF4A, AFP was significantly higher, similar to HLC-7, but not other non specific PDX1, Ep CAM, and CK7. liver specific function detection results showed that most of the experimental results showed that the majority of them were found. 5 can take LDL, about 40% can absorb ICG; PAS staining results suggest that about 60% of HLC-5 can synthesize glycogen. The urea synthesis experiment shows that HLC-5 has the ability to synthesize urea. Compared with the control group, the results of.3.4 after MI RNA are statistically significant: the cell morphology of each group is not obviously changed after 7 days of transfection; RT-PCR The results showed that the m RNA levels of ALB, HNF4A, AFP, CYP3A4 and TF were not significantly different from those of the control group. LDL uptake experiments also showed that 4 mi RNA induced cells failed to successfully absorb the LDL.4. acute liver damage model. The acute liver injury model was successfully established. Compared with the saline treatment group, the level of albumin increased after HLC-5 and HLC-7 transplantation, the level of transaminase decreased and the serum results were obviously improved; HE staining suggested the improvement of liver tissue structure. The results of inflammation alleviating.5. acute liver failure model showed that high concentration CCl4 treatment was 1 days after HE staining results. The liver tissue structure was severely damaged and inflammatory cells infiltrated. Observation of survival within a week was found, compared with the saline control group, HLC-5 and HLC-7 could significantly improve the survival time of nude mice. There was no significant difference between the HLC-5 and the HLC-7 two groups, indicating that HLC-5 had a similar function to HLC-7 in the body. [Conclusion] this study The results show that 5 kinds of MI RNA (MI R-122148a, 424542-5p and 1246) are the best combinations to induce the differentiation of umbilical cord mesenchymal stem cells into hepatocyte like cells. The induced HLC-5 not only has the function of hepatocyte in vitro, but also can play a similar damage repair function with HLC-7 in the animal model, and can significantly improve the liver failure in nude mice. This provides an experimental basis for the application of hepatocyte like cells in biological artificial liver. The specific mechanism of MI RNA regulation of transdifferentiation and the cell characteristics of HLC-5 need to be further explored.
【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R575.3

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 本刊編輯部;;我國(guó)首家間充質(zhì)干細(xì)胞庫在天津落成[J];中國(guó)藥業(yè);2006年07期

2 張?chǎng)?趙桂秋;;間充質(zhì)干細(xì)胞在眼科領(lǐng)域的研究與應(yīng)用[J];中國(guó)組織工程研究與臨床康復(fù);2009年06期

3 史春夢(mèng);;間充質(zhì)干細(xì)胞表述中需要注意的幾個(gè)問題[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2009年14期

4 瞿海龍;邊劍飛;張冰;王穎;周英蓮;;間充質(zhì)干細(xì)胞臨床應(yīng)用的前景與困惑[J];醫(yī)學(xué)研究與教育;2011年05期

5 郭子寬;;間充質(zhì)干細(xì)胞及其臨床應(yīng)用中的幾個(gè)問題[J];中國(guó)組織工程研究;2012年01期

6 李炳堯;武曉云;吳巖;;間充質(zhì)干細(xì)胞的分離與培養(yǎng):從實(shí)驗(yàn)室到臨床[J];中國(guó)組織工程研究;2013年14期

7 吳實(shí);鄧列華;;皮膚間充質(zhì)干細(xì)胞在促進(jìn)皮膚愈合中的作用[J];實(shí)用皮膚病學(xué)雜志;2013年03期

8 吳清法,王立生,吳祖澤;間充質(zhì)干細(xì)胞的來源及臨床應(yīng)用[J];軍事醫(yī)學(xué)科學(xué)院院刊;2002年03期

9 黃定強(qiáng);間充質(zhì)干細(xì)胞的研究進(jìn)展[J];國(guó)外醫(yī)學(xué)(耳鼻咽喉科學(xué)分冊(cè));2003年03期

10 付文玉,路艷蒙,喬?hào)|訪,樸英杰;運(yùn)用組織工程學(xué)原理構(gòu)建間充質(zhì)干細(xì)胞的三維培養(yǎng)體系[J];濰坊醫(yī)學(xué)院學(xué)報(bào);2003年03期

相關(guān)會(huì)議論文 前10條

1 陳可;王丁;韓之波;朱德林;韓忠朝;;人臍帶間充質(zhì)干細(xì)胞體外發(fā)揮免疫活性的研究[A];第12屆全國(guó)實(shí)驗(yàn)血液學(xué)會(huì)議論文摘要[C];2009年

2 金明順;張毅;賈秀芬;周燕華;閆妍;劉慧雯;;小鼠脂肪間充質(zhì)干細(xì)胞的分離、培養(yǎng)以及多潛能分化的研究[A];中國(guó)解剖學(xué)會(huì)第十一屆全國(guó)組織學(xué)與胚胎學(xué)青年學(xué)術(shù)研討會(huì)論文匯編[C];2009年

3 李爭(zhēng)艷;劉楊;翟麗麗;楊迷玲;王立峰;;間充質(zhì)干細(xì)胞在腫瘤發(fā)展過程中的作用[A];中華醫(yī)學(xué)會(huì)病理學(xué)分會(huì)2009年學(xué)術(shù)年會(huì)論文匯編[C];2009年

4 張彥;李尚珠;;間充質(zhì)干細(xì)胞在血管工程中的機(jī)制及應(yīng)用[A];2009全國(guó)中西醫(yī)結(jié)合周圍血管疾病學(xué)術(shù)交流會(huì)論文集[C];2009年

5 石玉;戴\戎;;周期性拉應(yīng)力對(duì)間充質(zhì)干細(xì)胞分化影響的研究[A];第九屆全國(guó)生物力學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2009年

6 黎嬌;朱爭(zhēng)艷;杜智;駱瑩;王鵬;高英堂;;人臍帶間充質(zhì)干細(xì)胞分泌物對(duì)肝細(xì)胞增殖和凋亡的影響[A];天津市生物醫(yī)學(xué)工程學(xué)會(huì)第30次學(xué)術(shù)年會(huì)暨生物醫(yī)學(xué)工程前沿科學(xué)研討會(huì)論文集[C];2010年

7 譚遠(yuǎn)超;Kevin;姜紅江;黃相杰;周紀(jì)平;;間充質(zhì)干細(xì)胞在骨傷疾病治療中的應(yīng)用[A];首屆全國(guó)中西醫(yī)結(jié)合骨科微創(chuàng)學(xué)術(shù)交流會(huì)暨專業(yè)委員會(huì)成立大會(huì)論文匯編[C];2011年

8 唐佩弦;;間充質(zhì)干細(xì)胞及其臨床應(yīng)用前景[A];第三屆全國(guó)血液免疫學(xué)學(xué)術(shù)大會(huì)論文集[C];2003年

9 戴育成;;間充質(zhì)干細(xì)胞的生物學(xué)特性和應(yīng)用[A];2005年華東六省一市血液病學(xué)學(xué)術(shù)會(huì)議暨浙江省血液病學(xué)學(xué)術(shù)年會(huì)論文匯編[C];2005年

10 胡琳莉;王昕榮;錢坤;李舟;楊薇;朱桂金;;小鼠間充質(zhì)干細(xì)胞向子宮內(nèi)膜分化的實(shí)驗(yàn)研究[A];第一屆中華醫(yī)學(xué)會(huì)生殖醫(yī)學(xué)分會(huì)、中國(guó)動(dòng)物學(xué)會(huì)生殖生物學(xué)分會(huì)聯(lián)合年會(huì)論文匯編[C];2007年

相關(guān)重要報(bào)紙文章 前10條

1 滿學(xué)杰;天津?yàn)I海新區(qū)建最大間充質(zhì)干細(xì)胞生產(chǎn)基地[N];新華每日電訊;2008年

2 滿學(xué)杰;津昂賽打造間充質(zhì)干細(xì)胞生產(chǎn)基地[N];醫(yī)藥經(jīng)濟(jì)報(bào);2008年

3 第三軍醫(yī)大學(xué)西南醫(yī)院輸血科 李忠俊 整理 吳劉佳;間充質(zhì)干細(xì)胞研究又見新方法[N];健康報(bào);2013年

4 上海生科院 上海交大醫(yī)學(xué)院健康科學(xué)研究所 曹楷;間充質(zhì)干細(xì)胞：干細(xì)胞中的孫悟空[N];上�？萍紙�(bào);2014年

5 記者　陳建強(qiáng);首家間充質(zhì)干細(xì)胞庫在津建成[N];光明日?qǐng)?bào);2006年

6 記者　馮國(guó)梧;細(xì)胞產(chǎn)品國(guó)家工程中心建設(shè)方案獲準(zhǔn)[N];科技日?qǐng)?bào);2007年

7 實(shí)習(xí)生 劉霞;間充質(zhì)干細(xì)胞有望用于面部整形[N];科技日?qǐng)?bào);2007年

8 本報(bào)記者 王新佳;我國(guó)“原始間充質(zhì)干細(xì)胞”注射液進(jìn)入臨床研究[N];中國(guó)高新技術(shù)產(chǎn)業(yè)導(dǎo)報(bào);2005年

9 馮國(guó)梧;全球首個(gè)臍帶間充質(zhì)干細(xì)胞庫規(guī)�；\(yùn)營(yíng)[N];科技日?qǐng)?bào);2008年

10 劉瑩清;全球首個(gè)臍帶間充質(zhì)干細(xì)胞庫泰達(dá)規(guī)模運(yùn)營(yíng)[N];北方經(jīng)濟(jì)時(shí)報(bào);2008年

相關(guān)博士學(xué)位論文 前10條

1 王皓;五指山小型豬OCT-4、SOX-2基因在骨髓間充質(zhì)與臍帶間充質(zhì)干細(xì)胞中的過表達(dá)研究[D];中國(guó)農(nóng)業(yè)科學(xué)院;2013年

2 孔德曉;間充質(zhì)干細(xì)胞及胰島素分泌細(xì)胞治療糖尿病的臨床及應(yīng)用基礎(chǔ)研究[D];山東大學(xué);2015年

3 董苑;SDF-1復(fù)合PDPBB的構(gòu)建及對(duì)間充質(zhì)干細(xì)胞趨化影響的研究[D];昆明醫(yī)科大學(xué);2015年

4 王磊;誘導(dǎo)胎盤來源間充質(zhì)干細(xì)胞向成牙骨質(zhì)細(xì)胞分化的實(shí)驗(yàn)研究[D];山東大學(xué);2015年

5 房賀;連接黏附分子A在促進(jìn)MSC修復(fù)CC14肝損傷中的作用及其機(jī)制[D];第二軍醫(yī)大學(xué);2015年

6 陳潔;間充質(zhì)干細(xì)胞外泌體對(duì)急性肺損傷小鼠的影響及相關(guān)機(jī)制的實(shí)驗(yàn)研究[D];中國(guó)人民解放軍醫(yī)學(xué)院;2015年

7 許婷;轉(zhuǎn)化生長(zhǎng)因子β1在蟑螂過敏原誘導(dǎo)的哮喘中對(duì)間充質(zhì)干細(xì)胞募集遷移的影響[D];南方醫(yī)科大學(xué);2015年

8 周雅麗;攜氧間充質(zhì)干細(xì)胞對(duì)胃癌化療效果的影響及其機(jī)制研究[D];蘭州大學(xué);2015年

9 沈舒寧;CKIP-1負(fù)調(diào)控間充質(zhì)干細(xì)胞成骨分化研究[D];第四軍醫(yī)大學(xué);2015年

10 姚惟琦;脂肪來源間充質(zhì)干細(xì)胞治療急性腎損傷[D];武漢大學(xué);2015年

相關(guān)碩士學(xué)位論文 前10條

1 顧立超;BTK抑制劑對(duì)間充質(zhì)干細(xì)胞miR-21的調(diào)節(jié)作用[D];河北聯(lián)合大學(xué);2014年

2 王文杰;鴨胚間充質(zhì)干細(xì)胞生物學(xué)特性及其移植修復(fù)肝損傷研究[D];中國(guó)農(nóng)業(yè)科學(xué)院;2015年

3 張猛;血管內(nèi)皮前體細(xì)胞對(duì)間充質(zhì)干細(xì)胞分化潛能的影響[D];石河子大學(xué);2015年

4 馬麗媛;利用MyoD基因誘導(dǎo)綿羊臍帶間充質(zhì)干細(xì)胞分化為成肌細(xì)胞的研究[D];東北林業(yè)大學(xué);2015年

5 宋維文;MicroRNA-133誘導(dǎo)綿羊間充質(zhì)干細(xì)胞分化為成肌細(xì)胞的研究[D];東北林業(yè)大學(xué);2015年

6 韓麗鑫;人臍帶來源的間充質(zhì)干細(xì)胞對(duì)耐維甲酸的早幼粒白血病細(xì)胞分化的研究[D];北京協(xié)和醫(yī)學(xué)院;2015年

7 陶利;綿羊臍帶和羊水間充質(zhì)干細(xì)胞的分禽培養(yǎng)及鑒定[D];內(nèi)蒙古大學(xué);2015年

8 陳以勝;亞低溫對(duì)顱腦創(chuàng)傷微環(huán)境下溫敏臍帶間充質(zhì)干細(xì)胞分化特性影響的研究[D];河北醫(yī)科大學(xué);2015年

9 夏勇;人臍帶間充質(zhì)干細(xì)胞抑制HepG2作用優(yōu)化方法探索[D];內(nèi)蒙古大學(xué);2015年

10 羅永慧;Pax6對(duì)大鼠脂肪間充質(zhì)干細(xì)胞的分化誘導(dǎo)作用及其應(yīng)用研究[D];成都醫(yī)學(xué)院;2015年

，

本文編號(hào)：1917467