Addition of stem cells from allogeneic donors accelerates engraftment and immune reconstitution after stem cell transplantation
Umbilical cord blood is a valuable source of hematopoietic stem cells. However, stem cell numbers are limited and there are significant delays in engraftment and immune reconstitution. Since full matching at the major histocompatibility complex (MHC) appears to be less critical in cord blood transplantation, one approach to increase the stem cell doses may be to combine cord blood units from different donors. The kinetics of hématologie engraftment and immune reconstitution were compared between one unit (2.5xlO')of T-depleted bone marrow cells from one single donor (C57BL/6 [H2b] or SJL/ J [H2s) and two units from different donors (C57BL/6+SJL/J) after transplantation into lethally irradiated (8.5Gy) BALB/c recipients (H2d). The dose of 2.5xl06 is the minimum required for rescuing the majority of the recipients. As shown in the figure, addition of one unit of stem cells from MHC mismatched allogeneic donor doubled the white blood counts on day+10 and +14. The differences were no longer significant on day +21, with the white counts only half of the pre-transplantation level. Similar effects were also observed on platelet count and hematocrit. The differences on peripheral T and B cell counts were first observed on day +21 and were not significant on day +60. Kinetics of chimerism demonstrated that cells from both donor (C57BL/6 and/or SJL/J) or recipient (BALB/c) contributed to myeloid and lymphoid reconstitution. However, when the stem cell doses in one single unit were increased to 1 x 107, the beneficial effects were not observed. The chimeras, containing cells from all three strains of mice survived in good health for more than 200 days after transplantation and were able to mount a recall immune response upon the challenge of ovalbumin in vivo. Our data suggest that addition of stem cells from MHC mismatched allogeneic donors is feasible and has beneficial effects on engraftment and immune reconstitution in a murine model of stem cell transplantation.
Chen, BJ; Cui, X; Chao, NJ
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