Hematopoietic Reconstitution of Mice Cord Blood Transplantation Combined with Bone Marrow Transient Hematopoietic Progenitor Cell

Abstract 4688

Umbilical cord blood has been increasingly used as a source of hematopoietic stem cells. However, fetal blood recipients had slower hematopoietic engraftment and impaired immune reconstitution. To accelerate myeloid and lymphoid recovery, we used an animal model of newborn blood modeled for cord blood (CB), along with transiently reconstituting progenitor cells from congenic bone marrow with recipients, as sources of stem cells. According to the previous reports that murine transiently reconstituting progenitor cells express the c-kit molecule, but not Sca-1 and lymphohematopoietic lineage markers, Lin^-sca-1^-c-kit⁺(c-kit⁺) were isolated by MACS method. c-kit⁺ cells population consisted of exclusively of medium- or large-sized blast-like cells, which displayed relatively low proliferative potential in vitro than Lin^-sca-1⁺ (sca-1⁺) population. After transplantation of CB from DBA/2 mice (H-2^d/d, CD45.2), with or without graded numbers of either c-kit⁺ or sca-1⁺ cells isolated from BDF1 mice (H-2^d/b, CD45.1) bone marrow into lethally irradiated CD45.2 congenic BDF1 mice, hematopoietic engraftment were dynamic investigated. The intermingled transplantation of CB and c-kit⁺ cells or sca-1⁺ cells at the dosages of 1×10⁴ or 2.5×10⁴ or 5×10⁴ to recipient mice leads to the quantity of white blood cells and platelets increased to 1×10⁹/L and 1×10¹²/L at day12, whereas the injection of CB alone resulted in day17. By 2 weeks post-transplantation, congenic BM-derived cells were dominantly found in granulocytes and B lymphocytes, while host cells were dominantly found in T lymphocytes in CB transplantation combined either with c-kit⁺cells or sca-1⁺ cells. In cotransplantation with CB and c-kit⁺cells – engrafted surviving mice, the degree of donor CB cells in the peripheral blood increased progressively over time, while congenic donor BM-derived cells decreased gradually. After 60 weeks cotransplantation with CB and c-kit⁺ cells, a complete chimerism frequency of CB–derived cells continued to maintain in granulocytes and B lymphocytes, while T lymphocytes were dominantly derived from CB. On the other hand, congenic bone marrow or host-derived cells were the dominant population and CB-derived cells in the peripheral blood were less than 10% after 60 weeks cotransplantation with CB and sca-1⁺cells. In conclusion, the cotransplantation of CB and congenic c-kit⁺ cells was able to accelerate early hematopoietic recovery due to congenic marrow cells. But complete or main chimerism of cord blood was formed without or with fewer residual cells of host origin and congenic BM origin in long-term multilineage reconstitution. Thus, this cotransplant model in vivo may be to bring useful information for improving hematopoietic and immune reconstitution in fetal blood recipients.