Objective: To explore the actions of keratinocyte growth factor (KGF) in leukemic mice allogeneic umbilical cord blood cell transplantation (UCBT) and elucidate its mechanism.
Methods: 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.
Results: 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).
Conclusion: 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.