Chen Guang-hua, Wang Yi, Qiao Shu-min, Feng Yu-feng, Zhu Zi-ling, Wu De-pei
Jiangsu Institute of Hematology, Key Laboratory of Thrombosis & Hemostasis, Ministry of Health, First Affiliated Hospital, Soochow University, Suzhou 215006, China.
Zhonghua Yi Xue Za Zhi. 2011 Nov 1;91(40):2863-7.
To explore the actions of keratinocyte growth factor (KGF) in leukemic mice allogeneic umbilical cord blood cell transplantation (UCBT) and elucidate its mechanism.
Peripheral blood drawn from the litters of C57BL/6 females was used as umbilical cord blood (UCB) graft. BALB/c mice were randomly divided into 7 groups (n = 12 each). The grouping was as follows. Control group 1, inoculated with leukemia. Control group 2, inoculated with leukemia at -4 d and total body irradiation (TBI) treatment. Control group 3, TBI treatment and reconstituted with 2 × 10(6) UCB-TNCs. Control group 4, injected with PBS subcutaneously, TBI treatment and reconstituted with UCB-TNCs with platelet transfusion. Control group 5, inoculated with leukemia, injected with PBS subcutaneously, TBI treatment and reconstituted with UCB-TNCs with platelet transfusion. Experiment group 1, injected with KGF subcutaneously, TBI treatment and reconstituted with UCB-TNCs with platelet transfusion. Experiment group 2, inoculated with leukemia, injected with KGF subcutaneously, TBI treatment and reconstituted with UCB-TNCs with platelet transfusion. The survival status, pathohistological changes, splenic lymphoid cell subsets and thymic output post-UCBT were compared between groups.
The survival time of control group 1 was (11.1 ± 1.5) days and all died of leukemia. The survival time of control group 2 was (11.5 ± 2.5) days and all died of aplasia. Five of 12 mice of control group 3 survived for 100 days and 7 mice died of visceral hemorrhage. Four of 12 mice of control group 5 survived for 100 days and 8 mice died of leukemia with a survival rate of 33.3%. Nine of 12 mice of experiment group 2 survived for 100 days and 3 mice died of leukemia with a survival rate of 75.0%. The survival was prolonged in experiment group 2 mice as compared with that of control group 5 mice (χ² = 4.996, P = 0.0254). The splenic T, NK and B cell counts in control group 4 mice at +35 d were (9.32 ± 0.48) × 10⁶, (1.59 ± 0.11) × 10⁶ and (18.74 ± 2.01) × 10⁶ respectively. While in group 6 mice at +35 d were (13.20 ± 1.14) × 10⁶, (1.75 ± 0.12) × 10⁶ and (20.36 ± 0.86) × 10⁶ respectively. The counts of T cell and NK cell of group 6 were higher than those of group 4 (both P < 0.05). The level of signal joint T-Cell receptor excision circles (sjTRECs) in control group 4 mice was (167 ± 17) copies per 10⁵ cells while that of experiment group 1 mice (228 ± 24) copies per 10⁵ cells. They were higher than that of control mice (P = 0.002).
Hematopoietic stem/precursor cells are abundant in full-term murine fetal peripheral blood. The infusion of KGF reduces the post-UCBT relapse of leukemia through the enhancement of thymic output.
探讨角质形成细胞生长因子（KGF）在白血病小鼠异基因脐血移植（UCBT）中的作用并阐明其机制。
取C57BL/6雌性小鼠产仔的外周血作为脐血（UCB）移植物。将BALB/c小鼠随机分为7组（每组n = 12）。分组如下。对照组1，接种白血病。对照组2，于-4 d接种白血病并进行全身照射（TBI）治疗。对照组3，进行TBI治疗并用2×10⁶个脐血单个核细胞（UCB-TNCs）进行重建。对照组4，皮下注射PBS，进行TBI治疗并用UCB-TNCs并输注血小板进行重建。对照组5，接种白血病，皮下注射PBS，进行TBI治疗并用UCB-TNCs并输注血小板进行重建。实验组1，皮下注射KGF，进行TBI治疗并用UCB-TNCs并输注血小板进行重建。实验组2，接种白血病，皮下注射KGF，进行TBI治疗并用UCB-TNCs并输注血小板进行重建。比较各组UCBT后的生存状态、病理组织学变化、脾脏淋巴细胞亚群及胸腺输出情况。
对照组1的生存时间为（11.1±1.5）天，全部死于白血病。对照组2的生存时间为（11.5±2.5）天，全部死于再生障碍。对照组3的12只小鼠中有5只存活100天，7只死于内脏出血。对照组5的12只小鼠中有4只存活100天，8只死于白血病，生存率为33.3%。实验组2的12只小鼠中有9只存活100天，3只死于白血病，生存率为75.0%。实验组2小鼠的生存期较对照组5小鼠延长（χ² = 4.996，P = 0.0254）。对照组4小鼠在+35 d时脾脏T、NK和B细胞计数分别为（9.32±0.48）×10⁶、（1.59±0.11）×10⁶和（18.74±2.01）×10⁶。而实验组6小鼠在+35 d时分别为（13.20±1.14）×10⁶、（1.75±0.12）×10⁶和（20.36±0.86）×10⁶。实验组6的T细胞和NK细胞计数高于实验组4（均P < 0.05）。对照组4小鼠中信号连接T细胞受体切除环（sjTRECs）水平为每10⁵个细胞（167±17）拷贝，而实验组1小鼠为每10⁵个细胞（228±24）拷贝。它们高于对照小鼠（P = 0.002）。
足月小鼠胎儿外周血中造血干/祖细胞丰富。输注KGF可通过增强胸腺输出减少UCBT后白血病的复发。
