TK/GCV治疗H-2半相合CD34^+和TK^+T细胞移植急性移植物抗宿主病研究(英文)

Experimental study on therapy of acute graft-versus-host disease using TK/GCV in H-2 haplotype matched CD34^+ cell mixed with TK^+T lymphocytes transplantation

目的探讨TK/GCV对H-2半相合CD34+细胞和TK+T细胞混合移植急性移植物抗宿主病(graftversushostdiseaseGVHD)疗效,为临床应用提供实验依据。方法从亲代雄性供鼠骨髓分离CD34+细胞,同时取脾脏T细胞转染TK基因。两者混合移植雌性F1代受鼠,每只受鼠输入CD34+细胞和TK+T细胞分别为1×105和1×107。移植0天或移植7d给予丙氧鸟苷(Ganciclovir,GCV)治疗,剂量为50mg/kg·d×7d腹腔注射。结果F1受鼠全部发生急性GVHD,对照组小鼠3周内全部死亡;GCV治疗组与对照组相比差异显著,P<0.01。移植0天或移植7d应用GCV小鼠生存时间分别为(26.6±4.8)d和(40.5±8.4)d。移植7d给予GCV疗效较好,P<0.05。结论TK/GCV系统对H-2半相合CD34+和TK+T细胞混合移植急性GVHD有较好治疗作用;GCV给予时间不同疗效有差异。

To study therapeutic effect of TK/GCV on acute graft-versus-host disease in H-2 haplotype matched murine CD34+ cell and TK+T lymphocytes transplantation, which provide experimental basis for clinical application of TK/GCV. CD34+ cells were separated from male parental donors, bone marrows, meanwhile T lymphocytes were gained from their spleens and transduced by retroviral vectors that carried thymidine kinase (TK) gene. The both were mixed and infused into female F1 recipient mice, CD34+ cells and TK+T lymphocytes each F1 recipient mouse received were 1×105 and 1×107, respectively. GCV was administered at the dosage of 50 mg/kg·d ×7 d by intraperitoneal injections 0 or 7 day after transplant. Acute GVHDs appeared in all mice, mice in control groups died 3 weeks after transplant. There was the significance between GCV groups and control groups (P <0.01). Survival of mice with GCV used on day 0 or 7 after transplant were (26.6±4.8) days and (40.5±8.4) days, respectively (P <0.05). Therapeutic effect of GCV was better used on day 7 compared with day 0 after transplant. [Conclusions] There is therapeutic effect of TK/GCV in H-2 haplotype matched murme CD34+ cell and TK+T lymphocytes transplantation. Therapeutic effect of TK/GCV depends on timing of GCV administration.