Distribution and Multiplication of Colony Forming Units From Bone Marrow and Spleen After Injection in Irradiated Mice

Lahiri, S. K.; Putten, L.M. van

doi:10.1111/j.1365-2184.1969.tb00334.x

Cited by 40 publications

(35 citation statements)

References 12 publications

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“…As there is no direct method for measuring the homing of HSCs, previous studies have used the homing of CFU-GMs to the bone marrow as a surrogate assay. [22][23][24][25] Using this assay, we show that the homing of G-CSFR Ϫ/Ϫ CFU-GMs is comparable to that of wild-type CFU-GMs (Figure 7). Although these data suggest that a defect in the homing of G-CSFR Ϫ/Ϫ HSCs is not responsible for the defect in engraftment, definitive proof will require the direct measurement of HSC homing.…”

Section: Discussionmentioning

confidence: 99%

“…HSC homing can be indirectly assessed by measuring the homing of CFU-GMs to the bone marrow. [22][23][24] Asaumi et al 25 showed that CFU-GMs are rapidly cleared from the blood and are detectable only in the bone marrow 24 hours after intravenous injection. We used this assay to compare the homing of wild-type and G-CSFR Ϫ/Ϫ CFU-GMs to the bone marrow.…”

Section: G-csfr Signals Are Required For the Normal Production Of Promentioning

confidence: 99%

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Pivotal role of granulocyte colony-stimulating factor in the development of progenitors in the common myeloid pathway

Richards¹,

Liu

Iwasaki

et al. 2003

Blood

136

104

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Granulocyte colony-stimulating factor (G-CSF) is the principal cytokine regulating granulopoiesis. G-CSF receptor-deficient mice (G-CSFR-/-) are neutropenic but have only a modest reduction of committed myeloid progenitors. Since it is likely that compensatory mechanisms are induced by the severe neutropenia present in G-CSFR-/- mice, a competitive repopulation assay was performed. These data show that under basal conditions, G-CSF drives nearly all of granulopoiesis through multiple mechanisms. Most importantly, G-CSFR signals regulate the production and/or maintenance of committed-myeloid progenitors. Surprisingly, G-CSFR signals also play a significant role in the regulation of primitive multipotential progenitors in vivo. The contribution of G-CSFR-/- cells to the hematopoietic stem cell compartment is modestly reduced. Moreover, a marked decrease in the contribution of G-CSFR-/- cells to other progenitors in the myeloid pathway, including erythroid and megakaryocytic progenitors, is observed. In contrast, relative to the hematopoietic stem cell compartment, the contribution of G-CSFR-/- cells to the lymphoid lineages is increased. These data suggest that G-CSFR signals may play a role in directing the commitment of primitive hematopoietic progenitors to the common myeloid lineage. Thus, regulation of G-CSF levels may provide a mechanism for directing primitive hematopoietic progenitors into the common myeloid lineage in response to environmental stresses. (Blood. 2003; 102:3562-3568)

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Section: Discussionmentioning

confidence: 99%

Section: G-csfr Signals Are Required For the Normal Production Of Promentioning

confidence: 99%

Pivotal role of granulocyte colony-stimulating factor in the development of progenitors in the common myeloid pathway

Richards¹,

Liu

Iwasaki

et al. 2003

Blood

136

104

View full text Add to dashboard Cite

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“…At the time of their deaths in the prior study, 5 the mice had 10 times the normal number of neutrophils than controls, and approximately 30% of injected cells had lodged to the BM within 24 hours, 5 an estimate that equals or exceeds normal BM seeding in many published studies. 3,[32][33][34][35][36][37][38][39][40] Our EPL Ϫ/Ϫ mice that received transplants of hemopoietic cells from donors treated with antibiotics survived and allowed us to assess their BM and blood hemopoietic reconstitution.…”

Section: Homing In Triple Selectin-deficient Recipients (Epl ؊/؊ )mentioning

confidence: 99%

Molecular pathways in bone marrow homing: dominant role of α4β1 over β2-integrins and selectins

Papayannopoulou

Priestley

Nakamoto

et al. 2001

Blood

176

156

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The specific retention of intravenously administered hemopoietic cells within bone marrow is a complex multistep process. Despite recent insights, the molecular mechanics governing this process remain largely undefined. This study explored the influence of ␤ 2 -integrins on the homing to bone marrow and repopulation kinetics of progenitor cells. Both antifunctional antibodies and genetically deficient cells were used. In addition, triple selectin-deficient mice were used as recipients of either deficient (selectin or ␤ 2 ) or normal cells in homing experiments. The homing patterns of either ␤ 2 null or selectin null cells into normal or selectin-deficient recipients were similar to those of normal cells given to normal recipients. Furthermore, spleen colonyforming units and the early bone marrow repopulating activity for the first 2 weeks after transplantation were not significantly different from those of control cells. These data are in contrast to the importance of ␤ 2 -integrin and selectins in the adhesion/migration cascade of mature leukocytes. The special bone marrow flow hemodynamics may account for these differences. Although early deaths after transplantation can be seen in recipients deficient in CD18 and selectin, these are attributed to septic complications rather than homing defects. However, when ␤ 2 -or selectin-null donor cells are treated with anti-␣ 4 antibodies before their transplantation to normal or selectin-deficient recipients, a dramatic inhibition of homing (>90%) was found. The data suggest that the ␣ 4 ␤ 1 /vascular cell adhesion molecule-1 pathway alone is capable of providing effective capture of cells within the bone marrow, but if its function is compromised, the synergistic contribution of other pathways, that is, ␤ 2 -integrins or selectins, is uncovered. IntroductionRestriction of the developing hemopoietic cells to certain anatomic sites within the body, that is, the extravascular spaces of the bone marrow (BM), signifies a unique microenvironment capable of providing not only anchorage to hemopoietic cells, but of transmitting signals enabling their proliferation and differentiation. The relationship of hemopoietic cells with their microenvironment is a highly dynamic one allowing further expansion on demand and, depending on the stimuli, the movement of cells in and out of their microenvironment. The ability of intravenously administered cells to re-establish connections within the BM environment is a clinically exploited example of that flexibility. As the sinusoidal endothelial cells separate the extravascular space from the circulation, intravenously administered cells need first to tether to the sinusoidal endothelium, then to firmly anchor themselves within the extravascular space through reversible adhesion and transmigration steps. Although several insights regarding the molecular pathways that guide these processes have been obtained, our knowledge of this complex process remains incomplete. Early reports suggest that galactose-and mannose-specific lectins (present...

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“…Other investigators have also shown that transplanted BM cells in an irradiated mouse model lodged in several organs, including BM, spleen, lung and liver, although their presence in all other organs except the BM and spleen was transient. [24][25][26] Our results show that most CD34 dull CD38 ϩ cells were hardly detectable in day 1 PB from allotransplant patients. Accordingly, it is suggested that most of these cells may be trapped in the above-mentioned organs.…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic progenitor cells from allogeneic bone marrow transplant donors circulate in the very early post-transplant period

Katayama

Mahmut

Takimoto

et al. 1999

Bone Marrow Transplant

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Summary:Despite the therapeutic efficacy of allogeneic bone marrow transplantation (allo-BMT), circulating hematopoietic progenitor cells after bone marrow transplantation have not been well characterized. In the present study, we focused on these 'post-transplant circulating progenitor cells (PTCPC)' which may be on their way to bone marrow. We analyzed the number of myeloid progenitor cells (CFU-GM) per 10 ml of peripheral blood (PB) on days 0 (just before transplantation), 1 (8-15 h after the completion of transplantation), 2, 3, 5, 7, 10, 14, 17, 21, 28 and 35 after allo-BMT in five transplant patients using a standard methylcellulose assay. In addition, high proliferative potential colony-forming cells (HPP-CFC) of the harvested donor bone marrow (BM) and day 1 PB of recipients were assayed in five patients. The origin of HPP-CFC from day 1 PB was analyzed by polymerase chain reaction of a DNA region containing a variable number of tandem repeats. The replating potential of these HPP-CFC was evaluated by a secondary colony assay. The proportion of CD38 negative cells among CD34 ؉ cells in the harvested BM and day 1 PB was evaluated by two-color flow cytometric analysis. The number of CFU-GM on day 1 ranged from 6 to 73/10 ml PB, and became undetectable on day 5. The reappearance of PTCPC was observed on day 14, along with hematopoietic recovery. The proportion of HPP-CFC among myeloid colonies from day 1 PB was significantly higher than that from harvested BM (44.3 ؎ 10.4% vs 11.3 ؎ 2.1%, respectively, n = 5, P = 0.0030). These HPP-CFC from day 1 PB were confirmed to be of donor origin. More than 90% of these HPP-CFC had replating potential. Two-color flow cytometric analysis revealed that the proportion of CD34 ؉ CD38 negative cells was significantly higher in day 1 PB than in the harvested BM (61.0 ؎ 16.5% vs 9.3 ؎ 3.5%, respectively, n = 7, P = 0.0002). These observations suggest that both primitive and committed transplanted myeloid progeniCorrespondence: Dr Y Katayama, Kobe West City Hospital, 2-4 Ichibancho, Nagata-ku, Kobe, Hyogo 653-0013, Japan Received 17 August 1998; accepted 19 October 1998 tor cells may circulate in the very early period following allo-BMT.

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Distribution and Multiplication of Colony Forming Units From Bone Marrow and Spleen After Injection in Irradiated Mice

Cited by 40 publications

References 12 publications

Pivotal role of granulocyte colony-stimulating factor in the development of progenitors in the common myeloid pathway

Pivotal role of granulocyte colony-stimulating factor in the development of progenitors in the common myeloid pathway

Molecular pathways in bone marrow homing: dominant role of α4β1 over β2-integrins and selectins

Hematopoietic progenitor cells from allogeneic bone marrow transplant donors circulate in the very early post-transplant period

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