Normal development of human fetal hematopoiesis between eight and seventeen weeks' gestation

OBJECTIVE: The aim of this study was to compare the hematologic compositions of fetal blood and liver and to phenotypically quantify the hematopoietic stem and progenitor cells during early human gestation. STUDY DESIGN: Fifty fetal blood samples and 50 fetal livers were collected at 10 to 17 weeks' gestation and 8 to 17 weeks' gestation, respectively. Investigations included fetal blood cell counts, determinations of red blood cell index values, and flow cytometric analyses of mononuclear cells. RESULTS: Fetal red blood cell, white blood cell, and platelet counts all increased with gestation, reflecting hematologic development. The proportion of normoblasts decreased dramatically with gestation. Individual mature red blood cells were larger and contained more hemoglobin during early gestation. Circulating and hepatic T lymphocytes increased in number shortly before the 13th week of gestation, which reflected thymic maturation. As a proportion fetal liver contained fewer T lymphocytes than did fetal blood (2.5% vs 18.6%; P = .003) but more CD34(+) hematopoietic stem and progenitor cells (17.5% vs 4.3%; P = .004). As a proportion, fetal liver contained more of the primitive CD34(+) and CD38(-) hematopoietic stem and progenitor cells than did fetal blood (32% vs 17%; P = .04). CONCLUSION: Both fetal blood and liver provide a rich source of hematopoietic stem and progenitor cells. Fetal liver provides a richer source of more primitive hematopoietic stem and progenitor cells than does fetal blood. For stem cell transplantation we suggest that fetal livers be collected before the 13th week of gestation, because T lymphocytes are present in much greater numbers in the fetal liver after this stage of gestation. Further, we suggest that in utero stem cell transplantations in fetuses with normal immune development should be performed before the 13th week of gestation.