Establishment Of A Murine Model Of Haploidentical Umbilical Cord Blood Transplantation And Its Related Study

Purpose: To establish a murine model of haploidentical umbilical cord blood transplantation and evaluate the characteristic of hematopoietic and immunological reconstitution.Methods: BDF1 recipient mice conditioned with high dose total body irradiation were transplanted with neonatal peripheral blood from DBA/2 mice through tail vein. Hematopoietic recovery and graft-versus-host disease ( GVHD ) were observed, and the engraftment level of neutrophils and lymphocytes from recipient's PB, BM, spleen and thymus were further detected by double-color flow cytometry.Results: After transplantation, WBC, PLT and Hb level rose significantly on day 18, 21 and 18 respectively. WBC and PLT recovered in normal range on day 29 and 36 respectively, while Hb was only partly retrieved until day 50. Long term survival rate of the recipient mice was 90%. There was no evidence of GVHD. Flow cytometry analysis on day 50 showed that the proportion of donor cells in nucleated cells of recipient PB was 88.1%, which contained 33.92% donor neutrophils and 16.83% donor T cells. Bone marrow nucleated cells are mostly neutrophils and B lymphocytes, which account for 42.94% and 37.24% respectively. 42.2% T cells were host origin in spleen, while T cells in thymus reached full chimerism. All CD11c+ dendritic cells derived from PB, BM and spleen achieved full or close to full chimerism.Conclusions: Each newborn peripheral blood unit yields enough progenitor cells to reconstruct the hematopoietic and immunologic system in haploidentical mice without causing GVHD. The close to full donor type chimerism was achieved. Effective reconstitution of immunocytes wan also reached both in lymphoid organs and peripheral.