Encouragement of Transplacental Stem Cell Transplantation.

Abstract

Human fetomaternal cell trafficking has been demonstrated to result in persistent microchimerism of the mother and offspring from 20–100% of pregnancies. The level of microchimerism is small but in disease states may compose up to 0.96% of some cell types. This microchimersim could conceivably have therapeutic affects by serving as a reservoir of normally functioning stem cells. In order to determine if the level of microchimerism could be increased we have begun to explore methods to increase the number of stem cells and permeability of the placental barrier. To assess the affect of increasing stem cell number, granulocyte colony-stimulating factor (GCSF) was delivered subcutaneously during mid-gestation in pregnant heterozygous mucopolysaccharidosis VII (MPS VII, a deficiency of beta-glucuronidase) mice. We observed an increase in the proportion of sections from mutant offspring with demonstrable beta-glucuronidase producing cells from ∼2% in PBS treated mice to ∼25% in GCSF treated mice. To assess the affect of increasing placental permeability, pregnant MPS VII heterozygous mice were injected IV with vascular endothelial growth factor (VEGF) and a transfusion of 1 × 107 GFP positive bone marrow cells. We observed an increase in circulating GFP positive cells to 0.15% of circulating cells in 25% of the offspring of high dose VEGF-treated animals. Analysis of mutant offspring from the VEGF-treated animals reveals a dose effect of VEGF with 61% of sections from the group receiving the highest dose having demonstrable beta-glucuronidase producing cells. These studies demonstrate a proof-of-principle that microchimerism can be increased substantially and subsequent studies will focus on optimizing this transfer and analyzing therapeutic effect.