發(fā)布時(shí)間：2018-02-25 02:01

  本文關(guān)鍵詞： 獼猴 間充質(zhì)干細(xì)胞 非清髓 單倍體造血干細(xì)胞移植　出處：《中國人民解放軍軍事醫(yī)學(xué)科學(xué)院》2005年博士論文　論文類型：學(xué)位論文

【摘要】：單倍體造血干細(xì)胞移植因?yàn)橐缭組HC屏障,存在移植物抗宿主病(GVHD)重、植入困難、致命性感染發(fā)生率高等問題,文獻(xiàn)報(bào)道非清髓性造血干細(xì)胞移植(NST)可通過形成供受者混合嵌合而誘導(dǎo)免疫耐受,相對(duì)減輕GVHD。間充質(zhì)干細(xì)胞(MSCs)是骨髓中的重要組分,可以分化為多種骨髓基質(zhì)細(xì)胞,支持造血,最近發(fā)現(xiàn)MSCs聯(lián)合造血干細(xì)胞移植可促進(jìn)植入、減輕GVHD。因此,本課題試圖聯(lián)合MSCs和非清髓性造血干細(xì)胞移植的優(yōu)點(diǎn),攻克單倍體造血干細(xì)胞移植的難關(guān)。 首先,從獼猴骨髓中分離、培養(yǎng)了MSCs,對(duì)其細(xì)胞表型和生物學(xué)特性進(jìn)行了鑒定,評(píng)價(jià)了MSCs輸注的安全性,發(fā)現(xiàn)MSCs無論靜脈輸注或骨髓內(nèi)輸注均未見毒性反應(yīng),可歸巢到異體骨髓并存活。接著將親子代配對(duì)的獼猴作為供受者,分為NST組(4例)和MSCs聯(lián)合NST組(4例),定期觀察兩組獼猴在造血恢復(fù)、嵌合水平、GVHD等,結(jié)果NST組造血恢復(fù)均較快(+8d),2/4例早期形成完全供者嵌合(FDC),出現(xiàn)Ⅱ-Ⅲ急性GVHD,1例移植排斥。MSCs聯(lián)合NST組1例早期即形成FDC,造血恢復(fù)較快(+6d),出現(xiàn)Ⅱ-Ⅲ急性GVHD;2例由混合嵌合(MC)逐漸轉(zhuǎn)為FDC,造血恢復(fù)較慢(+13d),未出現(xiàn)GVHD。 以上結(jié)果提示MSCs聯(lián)合單倍體NST移植可以促進(jìn)植入,減輕GVHD,可能是解決單倍體造血干細(xì)胞移植的一個(gè)新策略。
[Abstract]:Haploid hematopoietic stem cell transplantation (HSCT) has many problems, such as serious graft-versus-host disease (GVHD), difficult implantation, high incidence of fatal infection and so on. It is reported that NSTs can induce immune tolerance through the formation of mixed chimerism in donor recipients. The relative reduction of GVHD. mesenchymal stem cells (MSCs) is an important component in bone marrow. NSTs can differentiate into various bone marrow stromal cells and support hematopoiesis. Recently, it has been found that MSCs combined with hematopoietic stem cell transplantation can promote implantation and alleviate GVHD. therefore, this paper attempts to combine the advantages of MSCs and non-myeloablative hematopoietic stem cell transplantation to overcome the difficulties of haploid hematopoietic stem cell transplantation. Firstly, MSCs were isolated from the bone marrow of rhesus monkey. The phenotypic and biological characteristics of MSCs were identified. The safety of MSCs infusion was evaluated. It was found that no toxic reaction was found in MSCs either intravenously or intramedullary infusion. Rhesus monkeys were divided into NST group (n = 4) and MSCs combined with NST group (n = 4). Results Hematopoietic recovery was faster in NST group (8 d / 2 / 4 cases with complete donor chimerism), 1 case with 鈪，

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