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Magnetic resonance imaging (MRI) can be used to distinguish bone marrow (BM) from cartilage and may therefore be used to measure BM volume in intact bones. We used MRI to measure the total human fetal BM volume in intact fetuses during the second trimester of pregnancy and determined the contribution of the individual bones to the total compartment. The total BM volume ranged from 934 microL at 17 to 18 weeks to 4563 microL at 22 to 23 weeks of gestation. The largest contributor to the total BM volume was the spine, constituting 26.4% +/- 2.7% of the total volume. By analyzing leukocyte content and percentages of CD34+ cells, lymphocytes, granulocytes, and monocytes of determined volumes, absolute numbers of these cell populations in BM could be measured. The cellular composition of the BM compartment did not significantly change throughout the second trimester of gestation. Absolute white blood cell counts per fetus increased from 111 x 10(6) at 16 to 17 weeks to 1229 x 10(6) at 21 to 22 weeks. The absolute numbers of CD34+ cells increased from 25 x 10(6) at 16 to 17 weeks to 256 x 10(6) at 21 to 22 weeks. Similar analysis of liver and spleen revealed comparable absolute numbers of CD34+ cells in BM and liver throughout the second trimester of gestation. In fetal liver, CD34+ cells differentiate into red cells, myeloid cells, and platelets, while lymphopoiesis mainly occurs in BM or spleen. Combining MRI and cell counts provides a method to quantify specific cell populations in fetal compartments. This study may enable better evaluation of fetal diagnostics and therapies.

Abstract: Administration of recombinant-human G-CSF (rhG-CSF) is highly efficient in mobilizing hematopoietic stem and progenitor cells (HSC/HPC) from the bone marrow (BM) toward the peripheral blood. This study was designed to investigate whether repeated G-CSF-induced HSC/HPC mobilization in mice could lead to a depletion of the bone marrow HSC/HPC pool with subsequent loss of mobilizing capacity. To test this hypothesis Balb/c mice were treated with a maximum of 12 repeated 5-day cycles of either 10 μg rhG-CSF/day or 0.25 μg rmG-CSF/day. Repeated administration of rhG-CSF lead to strong inhibition of HSC/HPC mobilization toward the peripheral blood and spleen after >4 cycles because of the induction of anti–rhG-CSF antibodies. In contrast, after repeated administration of rmG-CSF, HSC/HPC mobilizing capacity remained intact for up to 12 cycles. The number of CFU-GM per femur did not significantly change for up to 12 cycles. We conclude that repeated administration of G-CSF does not lead to depletion of the bone marrow HSC/HPC pool. [Copyright &y& Elsevier]

Objective: Umbilical cord blood (UCB) is considered as an attractive alternative source of hematopoietic stem cells for allogeneic stem cell transplantations in patients who lack human leukocyte antigen (HLA)-matched donors. However, the low cell dose adversely affects hematopoietic recovery and therefore limits application of UCB transplantation in adults. Transplantation of multiple UCB units could be a strategy to overcome cell dose limitations. Materials and Methods: To investigate the effect of double cord transplantation, nonobese diabetic/severe combined immunodeficient mice were transplanted with human hematopoietic progenitor cells (CD34+) derived from two UCB units with HLA disparity. Human cell engraftment and donor origin was determined by flow cytometry. Results: Double CB transplantation resulted in increased engraftment levels in the bone marrow and peripheral blood in comparison with recipients of a single unit. Because this effect could be due to the higher cell dose (2.105 vs 1.105 cells), double CB transplantation was compared with single units containing equal cell numbers (2.105). In some cases, engraftment levels in recipients of single units containing 2.105 cells were significantly higher than after transplantation of 1.105 cells. These engraftment levels were similar to those observed after double CB transplantation. Chimerism analysis indicated that increased engraftment in recipients of two units was predominantly derived from one unit, whereas in other cases the contribution of the two units was similar. Conclusion: These results indicate that engraftment may be enhanced by addition of a second unrelated CB that might be attributed to a cell dose effect or due to a graft-facilitating effect. [Copyright &y& Elsevier]

: ObjectiveIn comparison with stem cell transplantation using bone marrow or cytokine-mobilized peripheral blood, cord blood transplantation is characterized by delayed engraftment, in particular platelet recovery. The differences in the kinetics of engraftment may be related to quantitative differences in the numbers of stem cells and megakaryocyte progenitor cells and/or to qualitative differences between megakaryocyte progenitor cells in these grafts. We compared the hematopoietic composition of these grafts and determined the distribution of mature and immature megakaryocyte progenitor cells in cord blood and mobilized peripheral blood and their in vitro kinetic behavior.: MethodsMegakaryocyte progenitor cell subpopulations from cord blood (CB) and mobilized peripheral blood (PBSC) were expanded in vitro in the presence of mpl-ligand. The developmental differences during expansion of megakaryocyte progenitors were analyzed by flow cytometry and progenitor assays.: ResultsWe found that the immature (CD34+/CD41−) subpopulation from CB contains more than 98% of all megakaryocyte progenitor cells, responsible for 99% of all megakaryocytic cells cultured during 2 weeks. The CB CD34+/CD41+ subpopulation shows no contribution to megakaryocytic cell formation. In contrast, in PBSC the mature (CD34+/CD41+) subpopulation contains 7% of all megakaryocyte progenitor cells. Moreover, CD34+ cells from CB and PBSC also showed distinct phenotypic differences during maturation in vitro. PBSC megakaryocyte progenitor cells transiently express both CD34 and CD41 during maturation in vitro, whereas CB progenitor cells transiently lack expression of both markers before differention into (CD34−/CD41+) megakaryocytic cells.: ConclusionThe in vitro data indicate the presence of different developmental stages of megakaryocyte progenitor cells in CB as compared to PBSC. These differences in composition and maturation between CB and PBSC may be related to the different kinetics of engraftment following transplantation of these stem cell sources. [Copyright &y& Elsevier]

Describes a patient with aplastic anemia who had a bone-marrow transplant but developed the disease 14 years later. The transplant from his HLA-genotypically identical sibling; Histology showing hypocellularity of the marrow.