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人骨髓間充質(zhì)干細胞端粒調(diào)控機制的研究

發(fā)布時間:2018-04-06 00:12

  本文選題:間充質(zhì)干細胞 切入點:端粒酶 出處:《浙江大學》2006年博士論文


【摘要】:間充質(zhì)干細胞(Mesenchymal stem cells,MSCs)具有高度擴增和自我更新能力及多向分化潛能,它能分化成為成骨細胞、軟骨細胞、脂肪細胞、造血支持基質(zhì)細胞、心肌細胞、神經(jīng)元細胞與神經(jīng)膠質(zhì)細胞。經(jīng)多次傳代培養(yǎng)后MSCs仍保持這種多向分化潛能。MSCs還具有低免疫原性特性;贛SCs這些特性,MSCs已經(jīng)被廣泛用于干細胞治療、受損組織修復(fù)和基因治療等臨床應(yīng)用試驗研究中。 雖然MSCs具有良好的臨床應(yīng)用前景,但其在骨髓內(nèi)的含量極低,僅占骨髓有核細胞的0.001%到0.01%,難以達到臨床有效治療應(yīng)用的需要。因此,為了獲得足夠數(shù)量的MSCs,需要進一步在體外進行培養(yǎng)、擴增。文獻報道,MSCs至少要經(jīng)過約10個細胞倍增時間(Populmion Doublings,PDs)擴增才能達到臨床有效治療的細胞數(shù)量。但是現(xiàn)有研究顯示MSCs在體外擴增能力有限,完成10個PDs培養(yǎng)后MSCs的生命周期的損失將超過50%,嚴重地影響了MSCs的自我更新、增殖、分化和歸巢能力,從而限制了其臨床應(yīng)用。因此,如何提高MSCs的分裂增殖能力、延長其生命周期是目前MSCs生物學特性理論研究和應(yīng)用研究中亟待解決的問題。 端粒是染色體末端由TTAGGG重復(fù)序列和相關(guān)結(jié)合蛋白質(zhì)組成的特殊保護性結(jié)構(gòu)。端粒的主要功能是防止染色體末端降解、融合、重組及DNA損傷修復(fù)系統(tǒng)的異常識別,以維持染色體的完整性和基因組的穩(wěn)定性。端粒與細胞的
[Abstract]:Mesenchymal stem cells (MSCs) are highly proliferative and self-renewing and have the potential to differentiate into osteoblasts, chondrocytes, adipocytes, hematopoietic support stromal cells, cardiomyocytes, osteoblasts, chondrocytes, adipocytes, hematopoietic support stromal cells and cardiomyocytes.Neurons and glial cells.The multidirectional differentiation potential of MSCs was maintained after multiple passages. MSCs also had low immunogenicity.MSCs has been widely used in stem cell therapy, repair of damaged tissue and gene therapy.Although MSCs has a good prospect of clinical application, its content in bone marrow is very low, which only accounts for 0.001% to 0.01% of the nucleated bone marrow cells, so it is difficult to meet the need of effective clinical treatment.Therefore, in order to obtain sufficient numbers of MSCs, it is necessary to further culture and amplify in vitro.It is reported that MSCs can only be amplified by popululmion Doublings PDs at least 10 cell doubling times in order to reach the number of cells that can be effectively treated clinically.However, existing studies show that the ability of MSCs amplification in vitro is limited, and the life cycle loss of MSCs after completing 10 PDs cultures will exceed 50%, which seriously affects the ability of self-renewal, proliferation, differentiation and homing of MSCs, thus limiting its clinical application.Therefore, how to improve the ability of mitotic proliferation and prolong the life cycle of MSCs is an urgent problem to be solved in the theoretical research and application of MSCs biological characteristics.Telomeres are special protective structures composed of TTAGGG repeats and associated binding proteins at the end of chromosomes.The main function of telomere is to prevent chromosome terminal degradation, fusion, recombination and abnormal recognition of DNA damage repair system in order to maintain chromosome integrity and genome stability.Telomere and cellular
【學位授予單位】:浙江大學
【學位級別】:博士
【學位授予年份】:2006
【分類號】:R329.2

【參考文獻】

相關(guān)期刊論文 前1條

1 溫冠媚,李浩威,肖慶忠,陳振光,張秀明,李艷,那曉東,項鵬,李樹濃;胎肝條件培養(yǎng)液體外誘導人骨髓間充質(zhì)干細胞定向分化為造血細胞的研究[J];中國病理生理雜志;2005年01期

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