Establishment of murine allogeneic umbilical cord blood cell transplantation model and study on the mechanism of keratinocyte growth factor enhancing immune reconstitution after transplantation / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the impact and mechanism of keratinocyte growth factor (KGF) on immune reconstitution post murine allogeneic umbilical cord blood transplantation (UCBT).</p><p><b>METHODS</b>Perpheral blood (PB) from 19.5-day embryos post-conception (E 19.5 d) mice was used as umbilical cord blood (UCB) graft. Thirty-two BALB/c mice were randomly assigned to 4 groups with 8 mice each in the first cohort UCBT. Mice were infused with PBS (control group) or 1 x 10(6) (group 1A), 2 x 10(6) (group 1B), 3 x 10(6) UCB mononuclear cells (MNCs) (group 1C), respectively. Twenty-four BALB/c mice were randomly assigned to 3 groups with 8 mice each in the second cohort UCBT. Mice were injected with 1 x 10(6) (group 2A), 2 x 10(6) (group 1B) or 3 x 10(6) (UCB) MNCs (group 2C). All mice received platelet transfusion on +8d. Sixteen BALB/c mice were randomly assigned to 2 groups with 8 mice each in the third cohort UCBT. Mice were injected s.c. with KGF (group 3) or PBS (control group) before TBI. All mice were injected with 2 x 10(6) UCB MNCs and were supported with platelet transfusion on +8 d. The survival time, splenic lymphoid cell subsets, sjTREC assay were observed after UCBT.</p><p><b>RESULTS</b>The 100-day survival of mice were 2, 3 and 3 in group 1A, 1B, 1C and 7, 8, 8 in group 2A, 2B, 2C, respectively. The splenic T, NKT, NK and B cell counts on +35 d were (9.57 +/- 0.74) x 10(6), (0.64 +/- 0.06) x 10(6), (1.43 +/- 0.10) x 10(6) and (19.13 +/- 1.50) x 10(6) in control group, respectively; while were (13.47 +/- 0.74) x 10(6), (0.89 +/- 0.03) x 10(6), (1.79 +/- 0.04) x 10(6) and (20.50 +/- 0.91) x 10(6) in group 3, respectively, being significantly higher than in control group. The sjTREC level was 182.2 +/- 10.7copies per 10(5) cells in control group; while was 224.2 +/- 9.6 copied per 10(5) cells in group 3, being significantly higher than in control group (P = 0.019).</p><p><b>CONCLUSIONS</b>Peripheral blood from E19.5d is rich in hematopoietic stem cells. A murine allogeneic UCBT model with platelet support on +8 d is established. KGF treatment can enhance thymic output and improve T cell immune reconstitution after UCBT.</p>