BACKGROUND AND OBJECTIVES: Characterization of the different sites of fetal hematopoiesis during the second trimester of pregnancy can provide important information for the timing of in utero stem cell transplantation (SCT), as an experimental treatment for congenital hematologic disorders. DESIGN AND METHODS: We analyzed the distribution of the different hematopoietic precursor cells in fetal blood, liver, bone marrow (BM), spleen and thymus from 66 fetuses between the ages of 13 to 23 weeks of gestation by flow cytometry and culture of hematopoietic progenitor cells (HPC) in semi-solid media. RESULTS: During the second trimester the percentages of CD34+ cells did not change and were 4.0% (1.0-12.0%) (median [min.-max.]) in blood, 16.5% (3.0-32.0%) in BM, 6.0% (2.0-16.0%) in liver, 5.0% (2.0-14.0%) in spleen, and 1.1% (0.9-3.0%) in the thymus. Each tissue contained all subsets of CD34+ cells at various levels. Within the CD34+ population, in BM the main sub-population was CD34+CD19+ (38% (11-67%)), in thymus CD34+ CD7+ (83% [45-98%]), and in blood and liver CD34+ CD33+ (57% (30-80%) and 48% (20-82%), respectively). In all tissues approximately 1 % of nucleated cells were non-committed CD34+ CD38- cells. The frequencies of both committed CD34+ cells and non-committed CD34+ CD38- cells were constant from 13 to 23 weeks in fetal blood, BM, liver and spleen. The frequencies of cultured HPC were high in fetal liver, low in fetal BM, and increasing in fetal blood. INTERPRETATION AND CONCLUSIONS: During the second trimester of gestation, all CD34+ subsets were present in each hematopoietic compartment at different levels. An exchange of stem cells between organs is likely, but no major shift of the hematopoietic stem cell compartment from the liver to other hematopoietic organs was found during the mid-trimester. No arguments for a specific time window for performing in utero SCT were found, but if engraftment of donor stem cells in the human fetus is influenced by competition of endogenous stem cells or fetal immune competence, in utero SCT should be performed as early as possible during fetal development.
BACKGROUND AND OBJECTIVES: Characterization of the different sites of fetal hematopoiesis during the second trimester of pregnancy can provide important information for the timing of in utero stem cell transplantation (SCT), as an experimental treatment for congenital hematologic disorders. DESIGN AND METHODS: We analyzed the distribution of the different hematopoietic precursor cells in fetal blood, liver, bone marrow (BM), spleen and thymus from 66 fetuses between the ages of 13 to 23 weeks of gestation by flow cytometry and culture of hematopoietic progenitor cells (HPC) in semi-solid media. RESULTS: During the second trimester the percentages of CD34+ cells did not change and were 4.0% (1.0-12.0%) (median [min.-max.]) in blood, 16.5% (3.0-32.0%) in BM, 6.0% (2.0-16.0%) in liver, 5.0% (2.0-14.0%) in spleen, and 1.1% (0.9-3.0%) in the thymus. Each tissue contained all subsets of CD34+ cells at various levels. Within the CD34+ population, in BM the main sub-population was CD34+CD19+ (38% (11-67%)), in thymus CD34+ CD7+ (83% [45-98%]), and in blood and liver CD34+ CD33+ (57% (30-80%) and 48% (20-82%), respectively). In all tissues approximately 1 % of nucleated cells were non-committed CD34+ CD38- cells. The frequencies of both committed CD34+ cells and non-committed CD34+ CD38- cells were constant from 13 to 23 weeks in fetal blood, BM, liver and spleen. The frequencies of cultured HPC were high in fetal liver, low in fetal BM, and increasing in fetal blood. INTERPRETATION AND CONCLUSIONS: During the second trimester of gestation, all CD34+ subsets were present in each hematopoietic compartment at different levels. An exchange of stem cells between organs is likely, but no major shift of the hematopoietic stem cell compartment from the liver to other hematopoietic organs was found during the mid-trimester. No arguments for a specific time window for performing in utero SCT were found, but if engraftment of donor stem cells in the human fetus is influenced by competition of endogenous stem cells or fetal immune competence, in utero SCT should be performed as early as possible during fetal development.