CHANGES IN THE GROWTH-PROPERTIES OF CD34(-) BONE-MARROW PROGENITORS DURING HUMAN FETAL DEVELOPMENT(), CD38()

We have previously described the isolation of separate populations of CD34(+), CD38(-) stromal and hematopoietic progenitors cells within fe tal bone marrow. The CD34(+), CD38(-), CD50(+), HLA-DR(+) population c ontained the majority of primitive hematopoietic progenitor cells, whe reas stromal progenitors were contained within the CD34(+), CD38(-), C D50(-), HLA-DR- population. In this study, we compared the frequencies and total numbers of clonogenic CD341(+), CD38(-) stromal and hematop oietic cells as a function of fetal gestational age using single-cell fluorescent-activated cell sorting (FAGS). At 14 weeks of gestation, 1 /500 fetal bone marrow mononuclear cells were primitive hematopoietic CD34(+), CD38(-), HLA-DR(+) progenitor cells, whereas 1/1,000 were str omal progenitors with the CD34(+), CD38(-), HLA-DR- phenotype. During fetal ontogeny there was a continuous, age-dependent decrease in the f requency of stromal progenitors, such that, at 24 weeks of gestation, only 1/100,000 of bone marrow cells had the CD34(+), CD38(-), HLA-DR(- ) phenotype and were clonogenic si romal cells when isolated by FACS. In contrast, 1/250 bone marrow cells in a 24-week fetus had the CD34(), CD38(-), HLA-DR(+) phenotype and were clonogenic hematopoietic prog enitors. The decrease in the frequency of stromal progenitors was a fu nction of both a decreased frequency of cells with the CD34(+), CD38(- ), HLA-DR(-) phenotype and a decrease in the growth potential of indiv idual with this phonotype. The total numbers of mononuclear cells and the total numbers of hematopoietic progenitors in two fetal femurs inc reased in parallel, 100-fold, between 14 and 24 weeks of gestation. In contrast, the total numbers of clonogenic CD34(+), CD38(-), HLA-DR(-) stromal progenitor cells remained constant during this period. Althou gh adult bone marrow samples contained stromal progenitor cells at a f requency of approximately 1/7,000 mononuclear cells, clonogenic stroma l cells with the CD34(+), CD38(-), HLA-DR(-) phenotype could not be is olated by single-cell FAGS from these samples. Thus, there are signifi cant differences between the frequencies and biologic characteristics of stromal and hematopoietic stem cells during fetal and postnatal ont ogeny. (C) 1995 by The American Society of Hematology.