H-2单倍体相合小鼠双供体造血干细胞移植模型的建立

发布时间：2018-02-16 05:05

本文关键词： H-单倍体相合双供体造血干细胞移植预处理　出处：《中国实验血液学杂志》2017年02期 　论文类型：期刊论文

【摘要】：目的:建立新的H-2单倍体相合小鼠双供体造血干细胞移植模型并与经典的造血干细胞移植进行比较,以减轻移植的相关并发症。方法:建立H-2单倍体相合小鼠双供体外周血造血干细胞移植模型并与8 Gy预处理移植组进行比较。在经典移植组给予CB6F1受鼠8 Gy TBI预处理,2 h内回输经G-CSF动员的供体(雄性C57)脾单个核细胞(spMNC)3×10~7;在双供体移植(DHSCT)组给予CB6F1受鼠2 Gy TBI,2 h内回输H-2单倍体相合小鼠双供体来源的spMNC共12×10~7(每个供体各6×10~7),依据供鼠组品系和性别不同,双倍体移植组又再分为3组:A组为雄性C57+雌性BALB/c,B组为雄性C57+雄性BALB/c,C组为雄性C57+雄性C3H。观察4组的造血重建、移植物植入、GVHD及存活情况。结果:经典移植组出现严重造血抑制,WBC1×10~9/L持续3-5d;A、B、C各组未出现造血抑制(WBC3×10~9/L)。经典移植组快速植入,1周达到外周血完全植入;A、B、C 3组1周达混合植入,2周达完全植入。经典移植组34 d GVHD发生率及致死率均为100%。双供体移植(DHSCT)组中34 d总体GVHD发生率及致死率分别为49.6%、50%(P0.01,P0.05);50 d分别为60.4%和81.2%,50 d总体存活率为50.9%。A、B、C各组的造血重建、供体植入、GVHD发生率、GVHD致死率、OS等均无显著差异(P0.05)。结论:采用2 Gy TBI预处理、双供者细胞输注、无GVHD预防,可使供体完全稳定植入、无造血抑制、GVHD发生率及死亡率明显减少;研究表明,H-2单倍体相合小鼠双供体造血干细胞移植模型成功建立。
[Abstract]:Objective: to establish a new model of double donor hematopoietic stem cell transplantation in H-2 haploid mice and compare it with classical hematopoietic stem cell transplantation (HSCT). Methods: the model of H-2 haploid matched mouse peripheral blood stem cell transplantation was established and compared with that of 8Gy preconditioning transplantation group. In the classical transplantation group, 8 Gy TBI was given to the CB6F1 recipient mice. The G-CSF mobilized donor (male C57) splenic mononuclear cell spspMNC3 脳 10 ~ (7) was treated within 2 h, and the spMNC from H-2 haploid matched mice (12 脳 10 ~ (7)) (6 脳 10 ~ (7)) per donor was given to CB6F1 recipient mice within 2 h. Donor strain and sex were different, The diploidy group was subdivided into 3 groups: male C57 female BALB / cnb group B was male C57 male BALB / cnC group C was male C57 male C3H.The hematopoietic reconstitution of 4 groups was observed. GVHD and survival of grafts. Results: severe hematopoietic inhibition was found in classical transplantation group WBC1 脳 10 ~ (9 / L) / L lasted 3 to 5 days. No hematopoietic inhibition was found in group C (WBC3 脳 10 ~ (9) / L). Rapid implantation of WBC3 脳 10 ~ (9 / L) / L was achieved in classical transplantation group. In the classic transplantation group, the incidence and mortality of GVHD on 34 days were 100. In the group of double donor transplantation, the overall incidence and mortality of GVHD were 49.6%, respectively. The overall survival rates of the three groups were 60.4% and 81.2 days, respectively. The hematopoiesis reconstitution of each group was observed. There was no significant difference in mortality rate and OS between donor implantation and GVHD. Conclusion: 2 Gy TBI preconditioning, double donor cell infusion and no GVHD prevention can make the donor implanted stably, and the incidence and mortality of GVHD without hematopoietic inhibition can be significantly reduced. The results showed that the double donor hematopoietic stem cell transplantation model of H-2 haploid mice was successfully established.
【作者单位】：军事医学科学院附属医院血液科;
【基金】：国家自然科学基金(81130054) 国家科技支撑计划(2012BAI38B02) 应用基础研究项目重点项目(BWS12J045) 重大新药创制(2013ZX09J13102-10C)
【分类号】：R457.7;R-332

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