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Title: A new source of stem cells in amniotic fluid and placenta in 1st trimester of pregnancy
Author: Moschidou, Dafni
ISNI:       0000 0004 2687 4419
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2009
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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.
Supervisor: Guillot, Pascale ; Wells, Dominic Sponsor: EU
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral