The repopulation potential of fetal liver hematopoietic stem cells in mice exceeds that of their liver adult bone marrow counterparts.

Varying, limiting numbers of unseparated or purified cells (Ly-5.1), either from 14.5-day-old fetal liver (FL) or from adult bone marrow (BM) were coinjected with 10(5) unseparated BM cells (Ly-5.2) into lethally irradiated adult C57B1/6 recipients (Ly-5.2). The kinetics of donor cell repopulation of the lymphoid and myeloid compartments by Ly-5.1+ donor hematopoietic stem cells (ie, competitive repopulation units [CRU]) were monitored at various time points after the transplantation by Ly-5 analysis of the peripheral white blood cells (WBC). Recipients that had received on average less than 2 adult BM or FL CRU did not show a significant difference in the level of donor-reconstitution when analyzed 4 weeks after the transplantation, However, at 8 and 16 weeks, the FL recipients showed a significantly higher percentage of donor-derived nucleated peripheral blood cells than did the recipients of adult BM cells. Analysis of individual mice showed that approximately 80% of the recipients of FL CRU showed an increase in mature WBC output between 4 and 8 weeks after transplantation, whereas this occurred in less than 40% in the recipients of adult BM cells. In addition to this effect on mature cell output, the cellularity of the reconstituted BM was significantly higher in recipients of FL CRU than in recipients of adult BM CRU, even at 7 to 9 months after transplantation, which is consistent with an increased clonal expansion of FL CRU. When marrow cells from primary recipients of FL CRU were injected into secondary recipients, a significantly higher percentage of these mice showed donor-reconstitution of their lymphoid and myeloid compartments (P < .01) and to a greater extent (P < .008) as compared with mice that had received marrow cells from primary recipients of similar numbers of adult BM CRU. Taken together, these results show that individual FL CRU exhibit a greater proliferative activity in vivo than similar cells from adult BM that is accompanied by a greater production of daughter CRU.

[1]  P. Lansdorp,et al.  A comparison of long-term repopulating hematopoietic stem cells in fetal liver and adult bone marrow from the mouse. , 1996, Experimental hematology.

[2]  A. Cumano,et al.  Emergence of multipotent hemopoietic cells in the yolk sac and paraaortic splanchnopleura in mouse embryos, beginning at 8.5 days postcoitus. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Lansdorp.  Telomere length and proliferation potential of hematopoietic stem cells. , 1995, Journal of cell science.

[4]  C B Harley,et al.  Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Strouboulis,et al.  Development of hematopoietic stem cell activity in the mouse embryo. , 1994, Immunity.

[6]  R. Hardy,et al.  Absence of MHC class II expression distinguishes fetal from adult B lymphopoiesis in mice. , 1994, Journal of immunology.

[7]  A. Fine.  Human Fetal Tissue Research: Practice, Prospects, and Policy , 1994, Cell transplantation.

[8]  C. Eaves,et al.  Amplification of Sca-1+ Lin-WGA+ cells in serum-free cultures containing steel factor, interleukin-6, and erythropoietin with maintenance of cells with long-term in vivo reconstituting potential , 1994 .

[9]  R. Auerbach,et al.  In vitro differentiation of B cells and myeloid cells from the early mouse embryo and its extraembryonic yolk sac. , 1994, Experimental hematology.

[10]  Connie,et al.  Amplification of Sca-1+ Lin- WGA+ cells in serum-free cultures containing steel factor, interleukin-6, and erythropoietin with maintenance of cells with long-term in vivo reconstituting potential. , 1994, Blood.

[11]  P. Lansdorp,et al.  Ontogeny-related changes in proliferative potential of human hematopoietic cells , 1993, The Journal of experimental medicine.

[12]  I. Weissman,et al.  Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells , 1993, The Journal of cell biology.

[13]  B. Imhof,et al.  At day 8-8.5 of mouse development the yolk sac, not the embryo proper, has lymphoid precursor potential in vivo and in vitro. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[14]  E. Cronkite,et al.  Self-renewal of the long-term repopulating stem cell. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[15]  S. Nishikawa,et al.  Expression and function of c-Kit in fetal hemopoietic progenitor cells: transition from the early c-Kit-independent to the late c-Kit-dependent wave of hemopoiesis in the murine embryo. , 1993, Development.

[16]  C. Jordan,et al.  Primitive hemopoietic stem cells: direct assay of most productive populations by competitive repopulation with simple binomial, correlation and covariance calculations. , 1993, Experimental hematology.

[17]  D. Frappaz,et al.  In utero transplantation of stem cells in humans: immunological aspects and clinical follow-up of patients. , 1992, Bone marrow transplantation.

[18]  C. Eaves,et al.  Quantitative assay for totipotent reconstituting hematopoietic stem cells by a competitive repopulation strategy. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[19]  D. Harrison,et al.  Effects of transplantation on the primitive immunohematopoietic stem cell , 1990, The Journal of experimental medicine.

[20]  I. Lemischka,et al.  Cellular and developmental properties of fetal hematopoietic stem cells , 1990, Cell.

[21]  I. Lemischka,et al.  Clonal and systemic analysis of long-term hematopoiesis in the mouse. , 1990, Genes & development.

[22]  C. Eaves,et al.  Retrovirus-mediated gene transfer to purified hemopoietic stem cells with long-term lympho-myelopoietic repopulating ability. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Richard J. Jones,et al.  Two Phases of Engraftment Established by Serial Bone Marrow Transplantation in Mice , 1989 .

[24]  P. Celano,et al.  Two phases of engraftment established by serial bone marrow transplantation in mice. , 1989, Blood.

[25]  S. Hellman,et al.  Loss of hematopoietic stem cell self-renewal after bone marrow transplantation. , 1989, Blood.

[26]  E. Cronkite,et al.  Pluripotent stem cells with normal or reduced self renewal survive lethal irradiation. , 1988, Experimental hematology.

[27]  I. Weissman,et al.  Purification and characterization of mouse hematopoietic stem cells. , 1988, Science.

[28]  G. Keller,et al.  Clonal fluctuation within the haematopoietic system of mice reconstituted with retrovirus‐infected stem cells. , 1987, The EMBO journal.

[29]  W A Buurman,et al.  Limiting dilution assays. Experimental design and statistical analysis. , 1987, Journal of immunological methods.

[30]  C. Eaves,et al.  Properties of the earliest clonogenic hemopoietic precursors to appear in the developing murine yolk sac. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[31]  D. Harrison,et al.  Ultimate erythropoietic repopulating abilities of fetal, young adult, and old adult cells compared using repeated irradiation , 1984, The Journal of experimental medicine.

[32]  Y. Kitamura,et al.  Presence of mast cell precursors in the yolk sac of mice. , 1983, Developmental biology.

[33]  D. Harrison.  Long-term erythropoietic repopulating ability of old, young, and fetal stem cells , 1983, The Journal of experimental medicine.

[34]  D. Harrison,et al.  Loss of stem cell repopulating ability upon transplantation. Effects of donor age, cell number, and transplantation procedure , 1982, The Journal of experimental medicine.

[35]  R. Humphries,et al.  Self-renewal of hemopoietic stem cells during mixed colony formation in vitro. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[36]  G. Hodgson,et al.  ORGANIZATION OF HAEMOPOIETIC STEM CELLS: THE GENERATION‐AGE HYPOTHESIS , 1979, Cell and tissue kinetics.

[37]  D. Harrison,et al.  Processing by the thymus is not required for cells that cure and populate W/WV recipients. , 1979, Blood.

[38]  D. Ogden,et al.  The fate of serially transplanted bone marrow cell populations from young and old donors. , 1976, Transplantation.

[39]  M. Moore,et al.  ANALYSIS OF PROLIFERATION AND DIFFERENTIATION OF FOETAL GRANULOCYTE‐MACROPHAGE PROGENITOR CELLS IN HAEMOPOIETIC TISSUE * , 1973, Cell and tissue kinetics.

[40]  E. P. Evans,et al.  Competitive in vivo proliferation of foetal and adult haematopoietic cells in lethally irradiated mice , 1972, Journal of cellular physiology.

[41]  H. Micklem.  CELL PROLIFERATION IN HAEMATOPOIETIC SPLEEN COLONIES OF MICE: DIFFERENCE BETWEEN COLONIES DERIVED FROM INJECTED ADULT BONE MARROW AND FOETAL LIVER CELLS , 1972, Cell and tissue kinetics.

[42]  R. Schofield.  A COMPARATIVE STUDY OF THE REPOPULATING POTENTIAL OF GRAFTS FROM VARIOUS HAEMOPOIETIC SOURCES: CFU REPOPULATION , 1970, Cell and tissue kinetics.

[43]  M. Moore,et al.  Ontogeny of the Haemopoietic System: Yolk Sac Origin of In Vivo and In Vitro Colony Forming Cells in the Developing Mouse Embryo * , 1970, British journal of haematology.

[44]  G. Cartwright,et al.  Quantitative studies of blood and bone marrow neutrophils in normal mice. , 1968, The American journal of physiology.

[45]  J. Till,et al.  ISOLATION OF VARIANT CELL LINES DURING SERIAL TRANSPLANTATION OF HEMATOPOIETIC CELLS DERIVED FROM FETAL LIVER. , 1964, Journal of the National Cancer Institute.