Transplantation · 1997
Evidence for engraftment of human bone marrow cells in non-lethally irradiated baboons.
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Fontes P, Rogers J, Rao A S, Trucco M, Zeevi A, Ricordi C, Fung J J, Starzl T E
Аннотация
BACKGROUND: Prior to organ harvesting, an attempt was made to modulate the donor's immune responses against prospective xenogeneic recipients by infusion of "recipient-type" bone marrow.
METHODS: For this purpose, baboons conditioned with total lymphoid irradiation were given 6 x 10(8) unmodified human bone marrow cells/kg body weight with no subsequent treatment.
RESULTS: Animals survived until they were euthanized at 18 months. Using primers specific for human chorionic gonadotrophin gene, the presence of human DNA was confirmed by polymerase chain reaction in the blood of one animal for up to 18 months after cell transplantation; in the other animal, xenogeneic chimerism became undetectable in the blood at 6 months after bone marrow infusion. However, tissue samples obtained from both animals at the time they were euthanized had evidence of donor (human) DNA. Additionally, the presence of donor DNA in individually harvested colonies of erythroid and myeloid lineages suggested that infused human bone marrow cells had engrafted across the xenogeneic barrier in both baboons.
CONCLUSIONS: Bone marrow transplantation from human to baboon leads to establishment of chimerism and modulation of donor-specific immune reactivity, which suggests that this strategy could be reproducibly employed to create "surrogate" tolerogenesis in prospective donors for subsequent organ transplantation across xenogeneic barriers.
METHODS: For this purpose, baboons conditioned with total lymphoid irradiation were given 6 x 10(8) unmodified human bone marrow cells/kg body weight with no subsequent treatment.
RESULTS: Animals survived until they were euthanized at 18 months. Using primers specific for human chorionic gonadotrophin gene, the presence of human DNA was confirmed by polymerase chain reaction in the blood of one animal for up to 18 months after cell transplantation; in the other animal, xenogeneic chimerism became undetectable in the blood at 6 months after bone marrow infusion. However, tissue samples obtained from both animals at the time they were euthanized had evidence of donor (human) DNA. Additionally, the presence of donor DNA in individually harvested colonies of erythroid and myeloid lineages suggested that infused human bone marrow cells had engrafted across the xenogeneic barrier in both baboons.
CONCLUSIONS: Bone marrow transplantation from human to baboon leads to establishment of chimerism and modulation of donor-specific immune reactivity, which suggests that this strategy could be reproducibly employed to create "surrogate" tolerogenesis in prospective donors for subsequent organ transplantation across xenogeneic barriers.