Prenatal Treatment of Beta-Thalassemia Using Amniotic Fluid Stem Cells in a Mouse Model

Title: Prenatal treatment of beta-thalassemia using amniotic fluid stem cells in a mouse model Congenital diseases are important causes of fetal and neonatal morbidity and mortality. Collectively they represent a large burden of disease. In utero transplantation (IUT) of allogeneic stem cells has cured fetuses with severe immunologic defects but not other genetic conditions, possibly because of the fetal immune response to the transplanted allogeneic cells or because they have no proliferative advantage. We have shown that amniotic fluid (AF) provides a source of autologous/congenic stem cells that can differentiate into haematopoietic and mesenchymal lineages. In clinical aspect, amniocentesis is easier and safer than cord blood sampling. Furthermore, the early timing offers us the opportunity to do early intervention. This project aims to define the potential of AF stem cells (AFSCs) for prenatal therapy of congenital disorders using β-thalassaemia as a disease target. β-thalassaemia is the most common genetically inherited condition in Taiwan caused by a reduction in β-globin chain production and thus defective haemoglobin. Patients suffer profound anaemia from birth, are dependent on stressful and expensive blood transfusions and iron chelation therapy, with only 30% eligible for curative bone marrow transplantation. Using the C57BL/6J HBB th3 mouse model of β-thalassaemia, we will study IUT using selected Ckit(+)/Lin(-) AFSCs from wild type (C57BL/6J) genetically labelling with green fluorescence protein (GFP). There will be intraperitonal or intravascular routes of injection into E14.5 thalassemia mice. Disease correction will be assessed by (i) neonatal survival (homozygous mice usually die prior to or at birth), (ii) level of anaemia and (iii) AFSC engraftment. AF may ultimately provide an autologous source of stem cells that can be used in prenatal treatment or be banked for postnatal therapy.

Project ID:PC9907-2124
External Project ID:NSC99-2314-B182A-097-MY3