Showing papers on "Haematopoiesis published in 1978"
TL;DR: The glucose-6-phosphate dehydrogenase types and chromosomes of hematopoietic and other tissues were determined in a woman with agnogenic myeloid metaplasia and provide strong evidence that it is of clonal origin.
445 citations
TL;DR: It is concluded from these and other experiments that H-2 antigens present on resident cells of the thymus determine the spectrum of specificity of T cells which mature in thatThymus and eventually make up the peripheral T- cell pool.
Abstract: After immunization, normal H-2 heterozygous mice (for example H-2(b) × H-2(d)) generate two populations of cytotoxic effector T cells, one specific for target cells expressing H-2(b)-plus-antigen and the other specific for H- 2(d)-plus-antigen. With a multideterminant antigen, these two populations have about the same activity. We show here that the H-2 type of resident cells in the thymus determines the H-2 preference of cytotoxic T lymphocytes. F(1)(B 10 × B 10.D2) (H-2(b) × H-2 (d)) mice were thymectomized, lethally irradiated, and reconstituted with T-cell-depleted syngeneic hematopoietic cells. Groups of such ATXBM mice were grafted subcutaneously with neonatal thymus lobes from parental mice, either B10 (H-2 (b)) or B10.D2 (H-2(d)). 2-3 mo later, the mice were immunized against the minor histocompatibility antigens on F(1)(BALB/c × BALB.B) cells and assayed for cytotoxic T-cell activity. H-2(b) × H-2(d) ATXBM mice with H-2(b) thymus grafts responded to antigen-plus-H-2(b) much better than to antigen-plus-H-2(d), and vice versa for the mice with H-2(d) thymus grafts. As judged by antiserum treatment, the effector cells were of F(1) origin. To explore the possibility that the “thymus preference” may have been due to suppression of T-cell activity, nonimmune spleen and lymph node cells from normal H-2(b) × H-2(d) mice and cells from H-2(b) × H-2(d) mice bearing a homozygous thymus were mixed 1:1 and immunized in adoptive transfer. The mixture responded to antigen-plus-H-2(b) and antigen-plus-H-2(d) equally well, demonstrating that the cells that showed a “thymus preference” could not suppress a response to antigen in association with the nonthymic H-2 type. We conclude from these and other experiments that H-2 antigens present on resident cells of the thymus determine the spectrum of specificity of T cells which mature in that thymus and eventually make up the peripheral T- cell pool.
313 citations
TL;DR: Assays showed that over one-half of the endosteal marrow cell population may be the colony-forming units, the CFU-S of Till and McCulloch, and high concentrations of stem cells could be obtained by means of the present isolation technique.
Abstract: Hematopoietic cells isolated from the endosteal bone surface, that is,the endosteal marrow cells, were found to consist mainly (60 to 80 percent) of lymphoid and late-stage normoblast-like cells Unlike the cells they resemble, the endosteal marrow cells showed an affinity for Sudan black, demonstrable nucleoli (Feulgen reaction), and an absence of hemoglobin Assays showed that over one-half of the endosteal marrow cell population may be the colony-forming units, the CFU-S of Till and McCulloch Thus, high concentrations of stem cells could be obtained from the endosteal bone surface by means of the present isolation technique
245 citations
TL;DR: Immediate stem cell proliferative capacities decline much more after one serial transplantation than after a lifetime of normal function.
Abstract: Marrow stem cell lines from old donors and those from young controls gave equally rapid rates of colony growth on spleens of irradiated mice. Old and young stem cell lines competed equally well with chromosomally marked marrow stem cells from a young donor in producing cell types that are stimulated by bleeding; old cells competed 70% as well as young in producing cell types stimulated by phytohemagglutinin (PHA) in vitro. After a single serial transplantation, the rates of colony growth declined 1.5- to 2.5-fold, and the ability to compete declined 2- to 4-fold for bleeding-stimulated and 4- to 10-fold for PHA-stimulated cells. Thus, immediate stem cell proliferative capacities decline much more after one serial transplantation than after a lifetime of normal function.
230 citations
TL;DR: Lewis rats given total lymphoid irradiation (TLI) accepted bone marrow allografts from AgB-incompatible donors and showed no clinical signs of graft-versus-host disease, and detectable levels of chimerism were not required for permanent survival.
Abstract: Lewis rats given total lymphoid irradiation (TLI) accepted bone marrow allografts from AgB-incompatible donors. The chimeras showed no clinical signs of graft-versus-host disease. Skin allografts from the marrow donor strain survived for more than 150 days on the chimeras. However, third-party skin grafts were rejected promptly. Although heart allografts survived more than 300 days in Lewis recipients given TLI and bone marrow allografts, detectable levels of chimerism were not required for permanent survival.
193 citations
TL;DR: A model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity is supported.
Abstract: The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferative quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cell progress in the continuum in one direction and such progression is not reversible.
154 citations
TL;DR: The exceptional permeability to MC 540 of leukemic leukocytes and immature hemopoietic precursor cells is described; since changes in MC 540 uptake appear to be correlated with cellular maturation during normal hemopOiesis, the retention of staining by leukedmic cells, some of which appear morphologically normal, may indicate of failure in membrane maturationDuring leukeMIC blood cell development.
147 citations
144 citations
TL;DR: Pokeweed mitogen‐stimulated suspension cultures of mouse spleen cells produced conditioned medium able to stimulate granulocyte‐macrophage, eosinophil and megakaryocyte colony formation in agar cultures of C57BL marrow cells and granulocytes‐macophage and erythroid colony formation on agar culture of CBA fetal liver cells.
Abstract: Pokeweed mitogen-stimulated suspension cultures of mouse spleen cells produced conditioned medium able to stimulate granulocyte-macrophage, eosinophil and megakaryocyte colony formation in agar cultures of C57BL marrow cells and granulocyte-macrophage and erythroid colony formation in agar cultures of CBA fetal liver cells. Medium conditioned by other mouse tissues stimulated only granulocyte-macrophage colony formation and this activity was not increased by the addition of pokeweed mitogen. Spleen cells stimulated by mixed leucocyte culture or concanavalin-A had a weak capacity to stimulate erythroid colony formation.
Production of the factors stimulating the four types of hemopoiesis was T-lymphocyte dependent and nu/nu spleen cells were inactive. Factor production was also dependent on adherent cells but evidence from rat-mouse combinations suggested that the T-lymphocytes actually produced the active factors.
Production of the four types of colony stimulating factors was radiosensitive (D0120–238 rads) and spleen cell populations of lighter buoyant density than 1.075 g/cm3 and sedimenting at 3.5–5.0 mm/hour were able to produce active conditioned media. Fractionation experiments failed to segregate spleen populations able to produce only one of the four stimulating factors.
Production of factors stimulating hemopoiesis by mitogen-stimulated lymphoid populations could be a process contributing to the control of hemopoiesis in vivo.
117 citations
TL;DR: The results strongly indicate that CFU‐mix represent a population of pluripotent hemopoietic stem cells in murine marrow, and are in close agreement with that reported for the spleen colony‐forming units.
Abstract: Murine marrow cells, when incubated in methylcellulose culture in the presence of erythropoietin and conditioned medium for two weeks, produced large macroscopic bursts containing normoblasts, macrophages, and often megakaryocytes. The clonal nature of these mixed colonies was supported by linearity studies and analyses of the percentages of constituent cells in different plating conditions. Time course observations and studies of the effects of L-cell-conditioned medium revealed that colony-forming cells for the mixed colonies (CFU-mix) are at earlier stages of hemopoietic development than burst-forming units (BFU-E). The mean of the modal sedimentation velocities of CFU-mix was 3.4 mm/hr and was in close agreement with that reported for the spleen colony-forming units. Almost none of the CFU-mix was in a DNA synthetic phase as measured by short-term exposure to tritiated thymidine. These results strongly indicate that CFU-mix represent a population of pluripotent hemopoietic stem cells in murine marrow.
TL;DR: It is demonstrated by double immunofluorescence, cocapping, and differential absorption studies that Thy-1 and BMLA are parts of the same molecule.
Abstract: Three approaches were used to demonstrate the presence of Thy-1 antigen on the surface of pluripotent hemopoietic stem cells in the rat. In the first, stem cells from fetal liver, neonatal spleen, and adult bone marrow were prevented from forming hemopoietic colonies in the spleens of irradiated recipients spleen (colony-forming unit assay) by incubation with antibodies to Thy-1 antigen. Highly specific rabbit heteroantiserum to purified rat brain Thy-1 antigen and mouse alloantisera to Thy-1.1-positive thymocytes were equally effective. This inhibition was neutralized by purified Thy-1 antigen. In a second series of experiments, Thy-1-positive and Thy-1-negative populations of nucleated bone marrow cells were separated by the FACS. All of the hemopoietic stem cell activity was recovered in the Thy-1-positive population. The stem cells were among the most strongly positive for Thy-1 antigen, being in the upper 25th percentile for relative fluorescence intensity. The relationships of Thy-1 antigen to the rat bone marrow lymphocyte antigen (BMLA) was shown in a third series of experiments. Rabbit anti-BMLA serum, which is raised against a null population of lymphocyte-like bone marrow cells, has been shown to have anti-stem cell activity. Here we demonstrate by double immunofluorescence, cocapping, and differential absorption studies that Thy-1 and BMLA are parts of the same molecule.
TL;DR: Direct evidence is reported for the presence of the antigens on bone marrow cells by separating them in a fluorescence-activated cell sorter according to their binding of anti-Ia-like (anti-p28,33) or anti-ALL antibodies.
Abstract: NORMAL and malignant B cells, some monocytes and blast cells from both the common (non-T, non-B) form of acute lymphoblastic leukaemia (ALL) and acute myeloblastic leukaemia (AML) share Ia-like antigenic determinants1–8. ALL cells, but not AML cells, can be further characterised by the expression of an ‘ALL-associated’ membrane antigen9,10. Although the ALL antigen and the Ia-like antigens on leukaemic blasts have at one time been regarded as candidate leukaemia-specific antigens, it has been suggested that both may be normal differentiation antigens of haematopoietic precursors, their expression in leukaemia reflecting the cellular origins of the disease2,7–11. In immunofluorescent studies combined with phase contrast examination, Ia-like antigens can be demonstrated on normal and leukaemic myeloblasts and some promyelocytes, but not on most promyelocytes and maturing granulocytic or erythroid cells7,8. The presence of Ia-like antigens on myeloid-committed stem cells is supported indirectly by results of functional assays in vitro which show the abolition of myeloid colony-forming cells (CFUc) by incubation with complement and heteroantisera to B cells12,13. Two disadvantages of the approach used in the latter experiments are, first, that the cells of interest are eliminated and no longer available for analysis, and second, that their functional inhibition does not necessarily establish that they carry the antigens in question, as the development of colonies involves stimulatory factors14,15 and auxiliary cells, whose activity, rather than CFUc per se, might be compromised by the antibodies used. We now report direct evidence for the presence of the antigens on bone marrow cells by separating them in a fluorescence-activated cell sorter (FACS), according to their binding of anti-Ia-like (anti-p28,33) or anti-ALL antibodies. Functional analysis of the resultant populations reveals that a proportion of human colony and cluster forming cells express the Ia-like hetero-antigen but not the ALL-associated antigen.
TL;DR: The evidence suggests a short range, stromal erythropoietic stimulatory factor which is lacking in the S1/S1d, regardless of which genotype was the irradiated, marrow‐injected host animal.
Abstract: Experiments were carried out with the intent of defining the nature of the microenvironmental defect which severely limits erythropoiesis in the spleen of the S1/S1d mouse. Chimeric spleens, half S1/S1d and half congenic +/+, supported erythropoiesis in the +/+ region but not in the S1/S1d region, regardless of which genotype was the irradiated, marrow-injected host animal. Implants of normal marrow stroma within the spleens of irradiated S1/S1d mice also supported normal proportions of erythrocytic and granulocytic hematopoiesis. Implants of normal spleen stroma, particularly the capsular portion, into unirradiated s1/s1d mice stimulated erythropoiesis originating from S1/S1d stem cells within and in the immediate vicinity of the implant. The evidence suggests a short range, stromal erythropoietic stimulatory factor which is lacking in the S1/S1d.
TL;DR: The ability of thyroid hormone to stimulate the erythroid committed progenitor cell does not seem to be a function of the state of differentiation of this cell.
Abstract: ANAEMIA is a frequent complication of thyroid dysfunction in man, and often remains unexplained, responding only to thyroid hormone replacement therapy1,2. Thyroid hormone has recently been shown to influence the rate of red blood cell and haemoglobin production3–7. In addition to stimulating erythropoietin (Ep) production3, thyroid hormone has been reported to act directly on haematopoietic precursors4,5. The enhancement of murine and canine in vitro erythroid colony growth by thyroid hormone6,7 suggests that this hormone may have a direct role in the modulation of erythroid proliferation. Studies of murine erythropoiesis support the existence of two distinct, age-structured, Ep responsive populations of committed erythroid precursor cells: the early committed erythroid burst forming unit (BFU-E) and the late committed erythroid colony forming unit (CFU-E)8. These populations are distinguished by cell volume, responsiveness to Ep, and proliferative capacity. The BFU-E, a cell which arises from the pluripotent stem cell soon after its commitment to the erythroid line and which has a high Ep-responsive proliferative capacity, seems to be the precursor of the CFU-E, a cell of lower proliferative capacity. Thyroid hormone has been shown to enhance in vitro erythroid colony formation by canine marrow cells, an effect that may be mediated by a receptor with β2-adrenergic properties7. Velocity sedimentation analysis revealed that colony-forming cells stimulated by this hormone sedimented more slowly than colony-forming cells responding to Ep alone7. Here, we have extended these studies to human marrow cells and have shown that the ability of thyroid hormone to stimulate the erythroid committed progenitor cell does not seem to be a function of the state of differentiation of this cell. Both CFU-E-derived and BFU-E-derived colony formation were enhanced by the hormone.
TL;DR: It is suggested that several clinically and karyotypically distinct leukaemias involve a similar lymphoid or pre-lymphoid cell type and that the ALL associated antigen is most likely a normal gene product of that cell type or lineage involved in the disease.
Journal Article•
TL;DR: It is shown that bone marrow from anti-mu-treated mice contains a population of cells with cytoplasmic IgM but which lack detectable cell-surface IgM, analogous to pre-B cells, defined in ontogenetic studies as the immediate precursors of B lymphocytes.
Abstract: Chronic treatment of mice from birth with anti-mu antibodies aborts development of B lymphocytes and plasma cells. In these studies we show that bone marrow from anti-mu-treated mice contains a population of cells with cytoplasmic IgM, but which lack detectable cell-surface IgM. These cells are analogous to pre-B cells, defined in ontogenetic studies as the immediate precursors of B lymphocytes. Pre-B cells from bone marrow of anti-mu treated mice retain their functional integrity, as evidenced by their ability to give rise to sIgM+, LPS-responsive lymphocytes in culture. We also show that cyclophosphamide treatment destroys pre-B cells and that recovery of pre-B cells in bone marrow precedes the regeneration of sIgM+ B lymphocytes. Generation of B lymphocytes in adult mice apparently occurs exclusively in the bone marrow because induction of extramedullary hemopoiesis in spleen was not accompanied by the appearance of pre-B cells in that organ.
Journal Article•
TL;DR: The toxicity of interferon to bone marrow was studied by the use of in vitro colony forming assays for hemopoietic cells and the effects of mouse interfer on the growth of CFUc and CFUe in murine bone marrow cells were comparable with those of fibroblast interferons on human cells.
Abstract: The toxicity of interferon to bone marrow was studied by the use of in vitro colony forming assays for hemopoietic cells. In the same study the relative inhibitory effects of two clinically common interferon preparations, leukocyte and fibroblast interferons, were compared with regard to their effect on both myeloid [colony-forming unit, culture (CFUc)] and erythroid [colony-forming unit, erythroid (CFUe)] progenitor cells. CFUe formation in human bone marrow cells in vitro appeared to be fairly resistant to both interferons. Only high doses of both interferons gave a marked inhibition of CFUe. However, the toxicity of leukocyte and fibroblast interferon was divergent for CFUe in human bone marrow. Leukocyte interferon appeared to be considerably more inhibitory for CFUe than was fibroblast interferon. The effects of mouse interferon, induced in L929 cells, on the growth of CFUc and CFUe in murine bone marrow cells were comparable with those of fibroblast interferon on human cells. The toxicity of human and murine interferon was species specific. Except for the toxicity of leukocyte interferon to CFUc in human bone marrow, the toxicity of interferon was marked only with concentrations on interferon far exceeding the amount necessary to produce an antiviral state in vitro.
TL;DR: It is reported that when mouse marrow cells are incubated in vitro with infectious plasma or tissue culture fluids containing the Friend virus complex, a substantial number of erythroid bursts appear 5 d after the initiation of the cultures.
Abstract: WHEN mouse haematopoietic cells are incubated in plasma clot or methyl cellulose cultures in the presence of erythropoietin (EP), at least two kinds of colonies are observed1–4. After 2 days, randomly distributed erythroid colonies (defined as a clone of eight or more benzidine-positive cells) appear1,2, and after 3–8 d of culture with higher concentrations of EP, larger colonies arise in clusters or ‘bursts’3,4. The cells of origin have been termed the colony-forming unit-erythroid (CFU-E)1 and burst-forming unit-erythroid (BFU-E)3,4, respectively. Erythropoiesis in mice is also increased considerably by the Friend virus complex5,6, which has been studied mostly in vivo although there are systems for the study of erythroid transformation in vitro soon after infection7–10. Nooter and Bentvelzen11, using methyl cellulose cultures, showed that mouse marrow cells, previously incubated in vitro with purified Rauscher leukaemia virus, develop more erythroid colonies than untreated control cells. Clarke et al.12, using the plasma clot method, observed erythroid colonies 2 d after incubation of mouse marrow cells with culture fluid from Friend virus infected monolayers of fibroblasts. These colonies were similar to EP-induced 2-d colonies in gross morphology and random distribution throughout the clot. Virus-induced bursts were not present in later stages of culture and erythroid colonies were not induced after incubation of marrow cells with plasma from Friend virus infected mice. We now report that when mouse marrow cells are incubated in vitro with infectious plasma or tissue culture fluids containing the Friend virus complex, a substantial number of erythroid bursts appear 5 d after the initiation of the cultures. The Friend virus complex consists of at least two biologically active viruses—the spleen focus-forming virus (SFFV) which is replication defective and essential for increased erythropoiesis in vivo, and a helper murine leukaemia virus (MuLV-F)13,14.
TL;DR: In this paper, Colony forming units (CFUc) giving rise to myelocytic colonies in methylcellulose cultures were found among non-adherent mononuclear cells of human cord blood with a frequency of one in 1678.
Abstract: . Colony forming units (CFUc) giving rise to myelocytic colonies in methylcellulose cultures were found among non-adherent mononuclear cells of human cord blood with a frequency of one in 1678. The number decreased markedly during the first 8 to 10 days of life. They were rarely detected in adult blood by this technique.
Journal Article•
TL;DR: The results indicate that the Thy-1 antigen is present on hemopoietic precursors and on at least some of their lymphoid (both T and B) and nonlymphoid descendants.
Abstract: The distribution and identity of Thy-1+ cells during ontogeny in the rat were examined by immunofluorescent and histologic techniques, and the relative amount of Thy-1 antigen on different cell types was assessed by quantitative absorption. Thy-1+ cells were subsequently studied by dual immunofluorescence for the simultaneous expression of either T or B lymphocyte markers. The results indicate that the Thy-1 antigen is present on hemopoietic precursors and on at least some of their lymphoid (both T and B) and nonlymphoid descendants. In addition, six serologically distinct subpopulations of lymphoid cells were identified, and their position in T and B cell maturational pathways is discussed.
TL;DR: A cell type sensitive to treatment in vitro with antitheta serum and complement that appeared to be required for a cure of the macrocytic anemia of the W/Wv mouse and its mechanism of action involves its effect on the pluripotent stem cell.
TL;DR: It is suggested that the clinical haematopoietic toxicity of trimethoprim‐sulphamethoxzole can be abrogated by simultaneous administration of folinic acid.
Abstract: The effect of trimethoprim and sulphamethoxazole on haematopoiesis was studied in vitro using cloning techniques for human and murine erythroid and granulocytic precursor cells. Trimethoprim was found to inhibit granulopoiesis and erythropoiesis in vitro in a dose-dependent fashion with approximately 50% inhibition of human erythroid and granulocytic colonies at a therapeutically achievable concentration of 7 micrograms/ml. Sulphamethoxazole was also shown to impair haematopoiesis in vitro. The inhibition caused by both these constituents of co-trimoxazole was completely reversed by folinic acid. The data suggest that co-trimoxazole can impair human haematopoiesis by inhibition of tetrahydrofolate synthesis. These observations suggest that the clinical haematopoietic toxicity of trimethoprim-sulphamethoxazole can be abrogated by simultaneous administration of folinic acid.
Journal Article•
TL;DR: The effects of lithium on colony formation were studied in cultures stimulated by humoral CSF, cultures in which monocytes were relied upon to synthesize CSF de novo and unstimulated cultures, where lithium enhanced the action of CSF but did not stimulate colony formation in the absence ofCSF.
Abstract: Lithium carbonate therapy is associated with polymorphonuclear leukocytosis. In vitro studies have shown that lithium ions stimulate formation of granulocytic colonies. In a study undertaken to determine how lithium acts, colony-forming cells uncontaminated by monocytes (which elaborate colony-stimulating factor [CSF] in vitro) were obtained by means of a two-step cell separation procedure. The effects of lithium on colony formation were then studied in (a) cultures stimulated by humoral CSF, (b) cultures in which monocytes were relied upon to synthesize CSF de novo and (c) unstimulated cultures. Lithium enhanced the action of CSF but did not stimulate colony formation in the absence of CSF. In monocyte-stimulated cultures, colony formation increased with lithium concentrations up to 1 mmol/L but this increase paralleled that in CSF-stimulated cultures and therefore was not due to increased CSF production by monocytes. At higher concentrations of lithium, colony formation decreased in the monocyte-stimulated cultures but increased in the CSF-stimulated cultures. A lithium concentration of 4 mmol/L gave the greatest enhancing effect on colony formation in CSF-stimulated cultures and a concentration greater than 1 mmol/L inhibited de novo synthesis of CSF by monocytes.
TL;DR: Cell-free extracts from human polymorphonuclear neutrophils inhibited rebound granulopoiesis in the bone marrow and spleen of mice pretreated with cyclophosphamide to remove endogenous PMN, demonstrating that inhibitory activity derived from PMN can control granulopsin in vivo.
TL;DR: The results indicate that leukemic mouse cells inhibit normal mouse-marrow stem cells by releasing a diffusible substance, and this inhibition occurs primarily at the level of the pluripotent stem cell.
Abstract: Inhibition of normal mouse hemopoietic stem cells by leukemic cells (C1498) was observed with use of in vitro agar and in vivo diffusion-chamber cultures. The C1498 cells were unresponsive to colony-stimulating activity, and, above a critical threshold, they inhibited normal granulocyte progenitors in agar culture. C1498 cells added to normal marrow in diffusion chambers progressively reduced granulocyte progenitors. The larger, more rapidly growing, C1498 cells showed the most inhibitory effect. Transmembrane culture of C1498 cells adjacent to normal marrow in double diffusion chambers for five to 14 days led to reduction of recovery of granulocyte progenitors (72 +/- 7 per cent of control) and pluripotent stem cells (45 +/- 7 per cent of control) from the normal marrow chambers. These results indicate that leukemic mouse cells inhibit normal mouse-marrow stem cells by releasing a diffusible substance, and this inhibition occurs primarily at the level of the pluripotent stem cell.
TL;DR: The data indicate that the B-lymphocyte colony-forming cells detected in spleen colonies are genuine members of the hemopoietic clone derived from the initiating hemopOietic stem cell (CFU-S).
Abstract: Spleen colonies produced by transplanting lethally irradiated mice with either 12 day fetal liver or adult bone marrow cells were found to contain B- lymphocyte colony-forming cells (BL-CFC) . The proportion of BL-CFC positive spleen colonies did not increase substantially between 8 and 14 days after transplantation, the range being 18-45 percent. However, the absolute number of BL-CFC per spleen colony varied considerably (between 1 and 10,318), although the majority of colonies contained less than 200 BL-CFC. Irrespective of the time after transplantation, smaller spleen colonies were found to have a higher frequency of BL-CFC than larger spleen colonies. To determine the possible clonal origin of BL-CFC from spleen colony- forming unit (CFU-S), CBA mice were injected with equal numbers of CBA and CBA T(6)/T(6) fetal liver or adult bone marrow cells. Analysis of 7-15-day spleen colonies demonstrated that 90 percent were either exclusively T(6) positive or T(6) negative and approximately equal numbers ofboth colony types were observed. B-lymphocyte colonies were grown and successfully karyotyped from 19 spleen colonies. When compared with the original spleen colony karyotype the B-lymphocyte colony cells karyotype was identical in all 19 cases. In 3 of the 19 colonies analyzed a mixture of T(6) positive and T(6) negative karyotypes was present and identical proportions of the karyotypes were present in the pooled B-lymphocyte colony cells and spleen colony cells. The data indicate that the B-lymphocyte colony-forming cells detected in spleen colonies are genuine members of the hemopoietic clone derived from the initiating hemopoietic stem cell (CFU-S).
TL;DR: A peroxidase activity was found in hairy cells, located always in the endoplasmic reticulum but not in the Golgi apparatus or in any granule, and appears to be closely related to that of tissue macrophages, activated blood monocytes, and other nonlymphocytic hematopoietic cells.
TL;DR: Erythroid colony formation in agar cultures of CBA cells was stimulated by the addition of pokeweed mitogen‐stimulated C57BL spleen conditioned medium and both 48‐hour colonies and day 7 large burst or unicentric erythroid colonies developed, together with many neutrophil and/or macrophage colonies.
Abstract: Erythroid colony formation in agar cultures of CBA cells was stimulated by the addition of pokeweed mitogen-stimulated C57BL spleen conditioned medium. Both 48-hour colonies (“48-hour benzidine-positive aggregates”) and day 7 large burst or unicentric erythroid colonies (“erythroid colonies”) developed, together with many neutrophil and/or macrophage colonies.
In CBA mice, the cells forming erythroid colonies occurred with maximum frequency (650/105 cells) in 10- to 11-day-old yolk sac and fetal liver but were present also in fetal blood, spleen and bone marrow. The frequency of these cells fell sharply with increasing age and only occasional cells (2/105 cells) were present in adult marrow. A marked strain variation was noted, CBA mice having the highest levels of erythroid colony-forming cells.
The erythroid colony-forming cells in 12-day CBA fetal liver were radiosensitive (Do 110–125 rads), mainly in cycle and were non-adherent, light density, cells sedimenting with a peak velocity of 6–9 mm/hr. These properties are similar to those of other hemopoietic progenitor cells in fetal tissues. The relationship of these apparently erythropoietin-independent erythroid colony-forming cells to those forming similar colonies after stimulation by erythropoietin remains to be determined.
TL;DR: Correlation analysis of numbers of colony-forming progenitor cells was used as an approach to the quantitation of human pluripotent stem cells and raised the possibility that the immediate progenitors of the blasts may not be any of the myelopoietic progensitor cells monitored in these studies.
Abstract: Correlation analysis of numbers of colony-forming progenitor cells was used as an approach to the quantitation of human pluripotent stem cells. Marrow specimens were obtained from 24 patients with untreated acute myeloblastic leukemia, 22 patients under treatment, and 29 patients with no hematologic malignant disease. Three classes of progenitor cells were assayed: burst-forming units dependent on erythropoietin (BFU-E), colony-forming units dependent on erythropoietin (CFU-E), and granulopoietic progenitors (CFU-C). Significant positive correlations between numbers of BFU-E, CFU-E, and CFU-C were found in all 3 groups of patients. In contrast, no such positive correlations were seen between marrow blasts and any of the classes of colony-forming progenitors. These results were compatible with a shared relationship of the colony-forming progenitors to a pluripotent cell of origin and raised the possibility that the immediate progenitors of the blasts may not be any of the myelopoietic progenitor cells monitored in these studies.