猕猴间充质干细胞联合非清髓单倍体造血干细胞移植的实验研究

发布时间：2018-02-25 02:01

  本文关键词： 猕猴 间充质干细胞 非清髓 单倍体造血干细胞移植　出处：《中国人民解放军军事医学科学院》2005年博士论文　论文类型：学位论文

【摘要】：单倍体造血干细胞移植因为要跨越MHC屏障,存在移植物抗宿主病(GVHD)重、植入困难、致命性感染发生率高等问题,文献报道非清髓性造血干细胞移植(NST)可通过形成供受者混合嵌合而诱导免疫耐受,相对减轻GVHD。间充质干细胞(MSCs)是骨髓中的重要组分,可以分化为多种骨髓基质细胞,支持造血,最近发现MSCs联合造血干细胞移植可促进植入、减轻GVHD。因此,本课题试图联合MSCs和非清髓性造血干细胞移植的优点,攻克单倍体造血干细胞移植的难关。 首先,从猕猴骨髓中分离、培养了MSCs,对其细胞表型和生物学特性进行了鉴定,评价了MSCs输注的安全性,发现MSCs无论静脉输注或骨髓内输注均未见毒性反应,可归巢到异体骨髓并存活。接着将亲子代配对的猕猴作为供受者,分为NST组(4例)和MSCs联合NST组(4例),定期观察两组猕猴在造血恢复、嵌合水平、GVHD等,结果NST组造血恢复均较快(+8d),2/4例早期形成完全供者嵌合(FDC),出现Ⅱ-Ⅲ急性GVHD,1例移植排斥。MSCs联合NST组1例早期即形成FDC,造血恢复较快(+6d),出现Ⅱ-Ⅲ急性GVHD;2例由混合嵌合(MC)逐渐转为FDC,造血恢复较慢(+13d),未出现GVHD。 以上结果提示MSCs联合单倍体NST移植可以促进植入,减轻GVHD,可能是解决单倍体造血干细胞移植的一个新策略。
[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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