Isolation and recovery of fetal cells from maternal venous blood is an exciting technology in order to develop a non-invasive prenatal diagnosis. The optimal fetal cell type to be isolated from maternal blood for clinical diagnosis of fetal aneuploides or inherited diseases is presently unknown. Fetal nucleated erythrocytes seem to be the best candidate, however, the efforts to isolate a sufficient, uncontamined number of erythroblasts failed and the current methodologic approaches are not capable of genetic diagnosis. The culture of fetal stem cells present in maternal blood is a promising alternative appoach. In order to obtain a proper number of fetal erythroid colonies (BFU-E) from maternal blood, we developed a methodology consisting of four steps: 1.) Twenty ml of peripheral blood are withdrawn from 25 voluntary pregnants between 11-16 weeks of gestation. Amniocentesis was performed for genetic analysis at 14-16 weeks. Blood was diluted 1:1 (v/v) with PBS + 0.6% ACD-A and then stratified on Ficoll-Paque (1.077 density) and centrifuged. The periphera blood mononuclear cells (PBMC) obtained were resuspended in PBS and the cells counted in a Burker chamber. 2. In order to enrich the stem cell population the miniMacs technique was used. The isolation of hemopoietic progenitor cells, present in PBMC, was performed by positive selection of CD34+ expressing cells. For miniMacs separation, CD34+ hemopoietic progenitor cells were indirectly magnetically labeled using an hapten conjugated primary monoclonal antibody and anti-hapten antibody coupled to miniMacs microbeads. The magnetically labeled cells were enriched on positive columns in the magnetic field. 3. Selectioned cells were seeded using a methylcellulose culture system. The methylcellulose (with Erythropoietin and others growth factors) allows the growing of human hemopoietic colonies and the differentiation of progenitors of interest. 4. The identification of fetal erythroid cells from those of maternal origin has been performed using FISH. The cells has been hybridised with the cromosome X-specific alpha satellite probe and Y chromosome specific DNA probe (DYZ1, Oncor) to identify male fetal cells. We have obtained a good recovery (> 90%), purity (> 50%) and enrichment of CD34 cells after the miniMacs technique. The enrichment of BFU-E colonies after culture was 100 times higher even. With the FISH technology male fetuses were correctly identified; the Y chromosome signals were observed in a sufficient number of interphase nuclei. Our results indicate that it is possible to promote “in vitro” the fetal stem cell growth and consequently to obtain a sufficient number of fetal cells to allow a non invasive prenatal diagnosis.