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.

[1]  C. Rodeck,et al.  Maternal tobacco exposure and cotinine levels in fetal fluids in the first half of pregnancy. , 1999, Obstetrics and gynecology.

[2]  L. Shields,et al.  Gestational age changes in circulating CD34+ hematopoietic stem/progenitor cells in fetal cord blood. , 1998, American journal of obstetrics and gynecology.

[3]  M. Divon,et al.  Immunophenotypic characterization of human fetal liver hematopoietic stem cells during the midtrimester of gestation. , 1997, American journal of obstetrics and gynecology.

[4]  J. Sampol,et al.  Quantitative analysis of leukocyte membrane antigen expression on human fetal and cord blood: normal values and changes during development. , 1997, Clinical immunology and immunopathology.

[5]  J. Dick,et al.  Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[6]  D. Liu,et al.  Gestational age and cell viability determine the effect of frozen storage on human fetal hematopoietic progenitor cell preparations. , 1996, Fetal diagnosis and therapy.

[7]  A. Medvinsky,et al.  Definitive Hematopoiesis Is Autonomously Initiated by the AGM Region , 1996, Cell.

[8]  O. Ringdén,et al.  Immunological capacity of human fetal liver cells. , 1994, Bone marrow transplantation.

[9]  K. Agematsu,et al.  Fetal liver T cell receptor gamma/delta+ T cells as cytotoxic T lymphocytes specific for maternal alloantigens , 1992, The Journal of experimental medicine.

[10]  K. Nicolaides,et al.  Blood leucocyte count in the human fetus. , 1992, Archives of disease in childhood.

[11]  L. Lanier,et al.  Ontogeny of human natural killer (NK) cells: fetal NK cells mediate cytolytic function and express cytoplasmic CD3 epsilon,delta proteins , 1992, The Journal of experimental medicine.

[12]  K. Nicolaides,et al.  Fetal T-lymphocyte subpopulations in normal pregnancies. , 1992, Fetal diagnosis and therapy.

[13]  N Catherine,et al.  Developmental hematopoiesis in normal human fetal blood. , 1991, Blood.

[14]  Y. Beuzard,et al.  Hematological Values of 163 Normal Fetuses between 18 and 30 Weeks of Gestation , 1986, Pediatric Research.

[15]  K. Nicolaides,et al.  Normal blood cell values in the early mid‐trimester fetus , 1985, Prenatal diagnosis.

[16]  C. Rodeck,et al.  Phenotypic analysis of fetal blood leucocytes: Potential for prenatal diagnosis of immunodeficiency disorders , 1982, Prenatal diagnosis.

[17]  C. Rodeck,et al.  Studies of circulating hemopoietic progenitor cells in human fetal blood. , 1982, Blood.

[18]  C. Rodeck,et al.  Development of cell-mediated lympholysis in human foetal blood lymphocytes. , 1980, Clinical and experimental immunology.

[19]  Professor Dr. Endre Kelemen,et al.  Atlas of Human Hemopoietic Development , 1979, Springer Berlin Heidelberg.

[20]  J. Playfair,et al.  The Leucocytes of Peripheral Blood in the Human Foetus , 1963, British journal of haematology.

[21]  J. M. Yoffey,et al.  Human Foetal Haemopoiesis I. The Cellular Composition of Foetal Blood , 1962, British journal of haematology.