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Stable long-term mixed chimerism achieved in a canine model of allogeneic in utero hematopoietic cell transplantation.

Abstract：

:Evidence supporting the efficacy of in utero hematopoietic cell transplantation (IUHCT) in a valid large animal model is needed prior to clinical application. The objective of this study was to establish clinically relevant levels of hematopoietic chimerism in a canine model of maternal-to-fetal IUHCT. We first assessed immune and hematopoietic ontogeny relevant to IUHCT in the canine model and identified 40 days' gestation (term 63 days) as a time point at the initiation of thymic selection, and prior to bone marrow hematopoiesis, that might be optimal for IUHCT. We next determined that intravascular administration of donor cells via intracardiac injection was far more efficient and resulted in much higher levels of donor cell engraftment than intraperitoneal injection. By applying these findings, we achieved stable long-term multilineage engraftment in 21 of 24 surviving recipients with an average level of initial chimerism of 11.7% (range 3% to 39%) without conditioning or evidence of graft-versus-host disease. Donor cell chimerism remained stable for up to 2 years and was associated with donor-specific tolerance for renal transplantation. The levels of donor cell chimerism achieved in this study would be therapeutic for many hematopoietic disorders and are supportive of a clinical trial of IUHCT.

journal_name

Blood

journal_title

Blood

authors

Vrecenak JD,Pearson EG,Santore MT,Todorow CA,Li H,Radu A,Bhatti T,Peranteau WH,Johnson MP,Flake AW

doi

10.1182/blood-2013-11-537571

subject

Has Abstract

pub_date

2014-09-18 00:00:00

pages

1987-95

issue

12

eissn

0006-4971

issn

1528-0020

pii

blood-2013-11-537571

journal_volume

124

pub_type

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