2011Journal of Clinical Medicine in PracticeRequires access

Establishment of a nonmyeloablative allogeneic peripheral blood stem cell transplantation model in mice and its related study

WU Jian-qiu

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Abstract

Objective To explore the effect of different types of infusion of allogeneic hematopoietic stem cells transplantation(HSCT) combined with donor lymphocytes infusion(DLI) on chimerism rate and incidence of graft-versushost disease(GVHD).Methods Female C57BL/6 mice(H-2b,B6) as recipients received total body irradiation(TBI),followed by the tail vein infusion(VI) or intra-bone marrow infusion(IBM) of allogeneic hematopoietic stem cells(3×107) transplantation(allo-HSCT) from mobilized male BALB/c with granulocyte-colony stimulating factor(rhG-CSF) and DLI(5×106),cyclophosphamide(200 mg/kg) was injected intraperitoneally two days later.Results Mixed chimeras was detected in all groups on day 7.The rate of mixed chimeras of IV-PBSCT-DLI group was much higher than the others.The GVHD was presented in the group of transplantation by VI,in which the IV-PBSCT-DLI group was more significant.However,there was no GVHD in the group which was transplanted by IBM.CD4+CD25+ obviously declined in IV-PBSCT-DLI group while rose in the IBM-PBSCT or IBM-PBSCT-DLI group.Conclusion Mixed-chimerism can be achieved by using a nonmyeloablative TBI and CTX-based conditioning regimen in combination with infusion of peripheral blood stem cells mobilized by rhG-CSF in fully H-2-mismatched recipient mice.DLI evidently promotes the donor chimers and the incidence of GVHD is reduced remarkably.Additionally,the mechanism involved in this process is probably associated with the changes of T-cell sub-group.

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Objective To explore the effect of different types of infusion of allogeneic hematopoietic stem cells transplantation(HSCT) combined with donor lymphocytes infusion(DLI) on chimerism rate and incidence of graft-versushost disease(GVHD).Methods Female C57BL/6 mice(H-2b,B6) as recipients received total body irradiation(TBI),followed by the tail vein infusion(VI) or intra-bone marrow infusion(IBM) of allogeneic hematopoietic stem cells(3×107) transplantation(allo-HSCT) from mobilized male BALB/c with granulocyte-colony stimulating factor(rhG-CSF) and DLI(5×106),cyclophosphamide(200 mg/kg) was injected intraperitoneally two days later.Results Mixed chimeras was detected in all groups on day 7.The rate of mixed chimeras of IV-PBSCT-DLI group was much higher than the others.The GVHD was presented in the group of transplantation by VI,in which the IV-PBSCT-DLI group was more significant.However,there was no GVHD in the group which was transplanted by IBM.CD4+CD25+ obviously declined in IV-PBSCT-DLI group while rose in the IBM-PBSCT or IBM-PBSCT-DLI group.Conclusion Mixed-chimerism can be achieved by using a nonmyeloablative TBI and CTX-based conditioning regimen in combination with infusion of peripheral blood stem cells mobilized by rhG-CSF in fully H-2-mismatched recipient mice.DLI evidently promotes the donor chimers and the incidence of GVHD is reduced remarkably.Additionally,the mechanism involved in this process is probably associated with the changes of T-cell sub-group.

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Available abstract

Objective To explore the effect of different types of infusion of allogeneic hematopoietic stem cells transplantation(HSCT) combined with donor lymphocytes infusion(DLI) on chimerism rate and incidence of graft-versushost disease(GVHD).Methods Female C57BL/6 mice(H-2b,B6) as recipients received total body irradiation(TBI),followed by the tail vein infusion(VI) or intra-bone marrow infusion(IBM) of allogeneic hematopoietic stem cells(3×107) transplantation(allo-HSCT) from mobilized male BALB/c with granulocyte-colony stimulating factor(rhG-CSF) and DLI(5×106),cyclophosphamide(200 mg/kg) was injected intraperitoneally two days later.Results Mixed chimeras was detected in all groups on day 7.The rate of mixed chimeras of IV-PBSCT-DLI group was much higher than the others.The GVHD was presented in the group of transplantation by VI,in which the IV-PBSCT-DLI group was more significant.However,there was no GVHD in the group which was transplanted by IBM.CD4+CD25+ obviously declined in IV-PBSCT-DLI group while rose in the IBM-PBSCT or IBM-PBSCT-DLI group.Conclusion Mixed-chimerism can be achieved by using a nonmyeloablative TBI and CTX-based conditioning regimen in combination with infusion of peripheral blood stem cells mobilized by rhG-CSF in fully H-2-mismatched recipient mice.DLI evidently promotes the donor chimers and the incidence of GVHD is reduced remarkably.Additionally,the mechanism involved in this process is probably associated with the changes of T-cell sub-group.

Key concepts: Medicine, Total body irradiation, Cyclophosphamide, Transplantation, Granulocyte colony-stimulating factor, Stem cell, Fludarabine, Haematopoiesis

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