Despite routing to GI and pulmonary tissues, donor cells fail to engraft after intra-amniotic or intravascular cell delivery in a healthy allogeneic mouse model

Abstract

In utero hematopoietic cell transplantation (IUHCT) exploits tolerogenic fetal immunologic development to facilitate engraftment of donor. Non-hematopoietic donor-derived cells have been described in both in-utero and post-natal models of hematopoietic cell transplantation. However, while epithelial routing has been reported, long-term engraftment following IUHCT has not been well studied. We utilized intra-amniotic (IA) or intravascular (IV) IUHCT to evaluate routing and engraftment within the pulmonary and gastrointestinal (GI) tract. High donor-cell viability is observed in the amniotic fluid 24 h after IA injection (mean 89.1 %). At 24 and 72 h, donor cells were present within the lumens of GI and pulmonary tissues and in the parenchyma of the liver, suggesting that donor cells route effectively to epithelial surfaces and hematogenous targets following IA injection. However, following IA delivery, long-term engraftment was not observed in peripheral blood, and there was no evidence of donor-derived cells in any target tissue including lung, bowel, or liver. Following IV injection, mean peripheral blood chimerism at terminal harvest was 23.86 % (SEM 12.44; Range 0.00–98.90). Following IV delivery, donor-derived cells were noted in the bowel, liver, and lung but not in the epithelium, suggesting these cells are circulating or tissue-resident leukocytes. Despite the routing of donor cells to multiple fetal sites, the IA injection was an extremely inefficient method for long-term engraftment in the hematopoietic niche, in organ parenchyma, or on epithelial surfaces. In contrast, despite IV IUHCT being able to consistently produce hematopoietic engraftment, epithelial engraftment was not observed, suggesting a limited role for IV IHUCT in epithelial disorders.