Haploidentical in utero hematopoietic cell transplantation improves phenotype and can induce tolerance for postnatal same-donor transplants in the canine leukocyte adhesion deficiency model.
Haploidentical in utero hematopoietic cell transplantation improves phenotype and can induce tolerance for postnatal same-donor transplants in the canine leukocyte adhesion deficiency model.
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DOI:
10.1016/j.bbmt.2008.11.034
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发表时间:
2009-03
期刊:
影响因子:
--
通讯作者:
Flake AW
中科院分区:
文献类型:
--
作者:
Peranteau WH;Heaton TE;Gu YC;Volk SW;Bauer TR;Alcorn K;Tuschong LM;Johnson MP;Hickstein DD;Flake AW
In utero hematopoietic cell transplantation (IUHCT) has been shown in the murine model to achieve low levels of allogeneic chimerism and associated donor specific tolerance permissive for minimal conditioning postnatal hematopoietic stem cell transplants (HSCT). In this pilot study, we investigate IUHCT in the canine leukocyte adhesion deficiency (CLAD) model. Haploidentical IUHCT resulted in stable low level donor cell chimerism in all dogs that could be analyzed by sensitive detection methodology (4 of 10) through 18 months of follow up. In the two CLAD recipients, low level chimerism resulted in amelioration and complete reversal of the CLAD phenotype respectively. Six recipients of IUHCT (5 carriers and 1 CLAD) subsequently received postnatal HSCT from the same haploidentical prenatal donor following minimal conditioning with 10 mg/kg Busulfan. Chimerism in 2 of 5 CLAD carriers that received HSCT increased from <1% pre-HSCT to sustained levels of 35 – 45%. Control animals receiving postnatal haploidentical HSCT without IUHCT had no detectable donor chimerism. These results demonstrate that haploidentical IUHCT in the CLAD model; 1) can result in low level donor chimerism that in CLAD dogs can prevent the lethal phenotype; and 2) can result in donor specific tolerance that can facilitate postnatal minimal conditioning HSCT.
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