Mesenchymal stromal cells (MSC) are multipotent cells found in fetal, neonatal and
adult tissues. Fetal MSC have advantageous characteristics over their adult
counterparts, and the regenerative potential of fetal blood MSC has recently been
shown in a model of skeletal dysplasia and renal failure. Although fetal blood MSC
can be isolated during ongoing pregnancy, the clinical effectiveness of using fetal
blood-derived MSC for prenatal fetal cell therapy is constrained by the invasive
nature of blood sampling procedure. With amniocentesis and chorionic villus
sampling (CVS), fetal MSC can be obtained with minimal invasion.
The aim of this study was to characterise stem cells from 1st trimester amniotic fluid
(AF) and placenta by comparing their phenotype with MSC from 1st trimester bone
marrow and 2nd trimester AF. Cells from all sources have similar immunophenotype,
express pluripotency markers and telomerase, but 1st trimester AF stem cells have
higher kinetics. The cells can differentiate into 3 lineages (bone, fat and cartilage),
form embryoid bodies (EB) in vitro and can be transfected with high efficiency
using non-viral methods.
The migration potential of fetal MSC was also investigated using in vitro migration
assays, to recapitulate the in vivo mechanisms involved in donor cell recruitment to
various tissues and delineate the pathways involved. Fetal blood MSC and AF stem
cells were shown to express CXCR4, the stromal cell-derived factor-1 (SDF-1)
receptor, intracellularly but not on the cell membrane and migrate to SDF-1
gradients and to osteoblast cultures derived from the Osteogenesis Imperfecta mouse
(oim), but not wild type bones. Pre-stimulation with oim plasma up-regulated
CXCR4 and increased chemotaxis to SDF-1 and oim bone.
Conclusively, 1st trimester AF and placenta are a new source of stem cells with great
potential for future cell therapy applications. Also, initial experiments indicate the
importance of the SDF-1/CXCR4 axis for stem cell recruitment to the site of injury.