Effect of in utero Infusion Route on Lymphocyte Distribution in Fetal Rat Tissues

Abstract

Infusion of cells into the fetus is a new form of intrauterine therapy for several genetic disorders. The effect of in utero infusion routes on labelled lymphocyte distribution in fetal rat organs was investigated. Fetuses, 14–16 days of gestation, were infused in utero with a Hoechst 33342 (bis-benzamide) labelled lymphocyte and FITC-labelled polystyrene bead mixture via four routes: intraperitoneal, intraplacental, intra-amniotic, and intravenous. The distribution within tissues was evaluated in frozen sections of placenta and fetal organs. Our results suggest that among the four routes tested, the intravenous route offered the possibility to reach easily fetal organs without any cell loss and yielded higher cell and bead concentrations in fetal organs, especially in the liver and in the kidney. In conclusion, the intravenous route seems to be appropriate for hematopoietic cell transplantation in the developing fetus.

Immune Tolerance Induction Using Fetal Directed Placental Injection in Rodent Models: A Murine Model

“…There have been several modes of antigen exposure utilized for delivering donor cells or genes during early gestation in animal models. These include intravascular[ 7 , 8 ], intracardiac[ 9 ], intraperitoneal[ 10 , 11 ], intraplacental[ 5 , 6 ], and intraamniotic injection. [ 12 ] Because of technical limitations, most of the studies were performed at later gestational stages than our study.…”

“…Historically, there have been previous studies utilizing intraplacental bone marrow transplantation in the early gestational mouse model. The classical studies of Fleischman and Mintz [ 5 , 6 ] demonstrated hematopoietic engraftment and chimerism after intraplacental injection of hematopoietic cells, but tolerance was not investigated. However, in those studies, the placenta was blindly injected, and delivery of the cells to the fetal circulation was inconsistent.…”