Effect of Age of Recipient Mice on Growth and Differentiation of Transplanted Bone Marrow Cells

Davis, M. L.; Upton, Arthur C.; Cosgrove, G. E.; Satterfield, L C

doi:10.3181/00379727-128-33216

Cited by 16 publications

(8 citation statements)

References 6 publications

(7 reference statements)

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“…Normal, untreated RFM/Un mice also had an increase in baseline platelet counts as they aged, with almost all the increase occurring during the first 25 weeks of life. 51 These results exactly parallel our observations.We propose the following hypothesis to explain our results. In control C57/Bl6 mice as well as in c-mpl Ϫ/Ϫ mice, the pool of HSCs spared by 5-FU enters into cycle, and subsequently, all myeloid progenitors are amplified.…”

supporting

confidence: 89%

supporting

confidence: 89%

“…50 In addition, another study found that the number of spleen colonies detected after lethal irradiation and bone marrow transplantation increased with the age of the recipient. 51 It is pertinent that the age-related increase in spleen colonies present in RFM/Un mice older than 30 weeks resulted almost entirely from increased numbers of MK colonies in the older mice. Normal, untreated RFM/Un mice also had an increase in baseline platelet counts as they aged, with almost all the increase occurring during the first 25 weeks of life.…”

Section: Discussionmentioning

confidence: 99%

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Thrombocytopenic c-mpl−/− mice can produce a normal level of platelets after administration of 5-fluorouracil: the effect of age on the response

Levin

Cocault²,

Demerens³

et al. 2001

Blood

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Administration of 5-fluorouracil (5-FU) to mice results in a marked increase in the level of circulating platelets in 10 days. Mice lacking Mpl, the receptor for thrombopoietin (TPO), are thrombocytopenic. To gain insight into the mechanism by which 5-FU produces such a substantial stimulation of platelet production, this study investigated whether 5-FU (150 mg/ kg) produced thrombocytosis in c-mpl ؊/؊ mice, thus establishing whether TPO was required for this response. A 5-to 6-fold increase in platelet levels in c-mpl ؊/؊ mice (to approximately 1000 ؋ 10 9 /L) was observed on days 20 and 25 after 5-FU injection. Thus, at the peak of the response, c-mpl ؊/؊ mice had platelet levels comparable to those in normal mice. Administration of 5-FU also produced thrombocytosis in previously splenectomized c-mpl ؊/؊ mice. Comparison of the platelet response to 5-FU in young (6-12 weeks) and old (33-46 weeks) c-mpl ؊/؊ mice found that older mice produced a much more marked response than younger mice, with a mean maximum platelet level of approximately 1700 ؋ 10 9 /L. To determine whether this increase in circulating platelets was preceded by an increase in hematopoietic progenitors, serial cultures of bone marrow and spleen were evaluated. A considerable increase in all colony types studied was observed on days 15 and 20 in spleens of c-mpl ؊/؊ mice, but no similar elevations were detected in bone marrow. These results indicate that c-mpl ؊/؊ mice can achieve a normal level of platelets after 5-FU injection, by means of a TPO-independent mechanism, and that they respond to 5-FU myelosuppression by producing large numbers of megakaryocytic, myeloid, and erythroid progenitors. IntroductionThe myelosuppressive agent fluorouracil (5-FU) produces a unique effect on megakaryocytopoiesis. Administration to mice of a single dose of 150 mg/kg results in gradual development of moderate thrombocytopenia, with the nadir in platelet count occurring approximately 4 to 8 days after administration. [1][2][3] Subsequently, the level of circulating platelets increases rapidly and thrombocytosis develops by day 10. 1-3 Platelet levels as high as 3000 ϫ 10 9 /L to 3500 ϫ 10 9 /L are reached (normal platelet count in mice is 1000 ϫ 10 9 /L to 1200 ϫ 10 9 /L), and thrombocytosis persists from approximately day 10 to day 19.Changes in platelet levels are associated with a marked increase in the number of megakaryocytes (MKs) in both bone marrow and spleen, with the increase occurring in the bone marrow after 7 or 8 days 3,4 but in the spleen only after 12 days. 4 A marked increase in the frequency and total numbers of MK colony-forming cells (MK-CFCs) occurs in the spleen concurrent with the period of thrombocytosis. 2 Despite the increase in spleen size and numbers of splenic MK-CFCs, it was shown that the spleen is not required for production of the marked thrombocytosis after administration of 5-FU. 3,5 The mechanism by which 5-FU produces marked thrombocytosis is unknown. The minimal brief reduction in the concentration of recognizable MK...

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supporting

confidence: 89%

supporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Thrombocytopenic c-mpl−/− mice can produce a normal level of platelets after administration of 5-fluorouracil: the effect of age on the response

Levin

Cocault²,

Demerens³

et al. 2001

Blood

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“…No differences in the incidence of marrow CFUs were found in mice until one (Kretchmar and Conover 1967;Davis et al 1968) and two years of age (Williams et al 1986). Neither any significant difference in the frequency of CFUs was seen in the spleen but the absolute numbers of CFUs showed a slight reduction in aged mice (Metcalf and Moore 1971;Silini and Andreozzi 1974;Boggs et al 1986).…”

Section: Discussionmentioning

confidence: 99%

Proliferation Activity and Number of Stromal (CFU-f) and Haemopoietic (CFUs) Stem Cells in Bone Marrow and Spleen of Rats of Different Ages

Vácek¹

2000

Acta Vet. Brno

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“…A longitudinal section was cut from the middle portion of each spleen and stained with haematoxylin and eosin. Colonies were identified and counted microscopically (Davis et al, 1968). The criteria of Curry & Trentin (1967) were used for identification of colonies.…”

Section: Microscopic Examination Of Spleen Coloniesmentioning

confidence: 99%

Colony‐forming Ability of Bone Marrow Cells of W Anaemic Mice on Macrophage Layer Formed in Peritoneal Cavity of Mice

et al. 1975

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The colony‐forming ability of haematopoietic cells of W anaemic mice was examined on the macrophage layer formed in the peritoneal cavity of mice. Bone marrow cells of W anaemic mice formed a considerable number of colonies on the macrophage layer, notwithstanding they did not form any colonies in the spleen of the same recipients. As the colony‐forming ability of the bone marrow cells was not reduced by the incubation with 3H‐thymidine, most of the cells which formed colonies on the macrophage layer seemed to stay in G0 state. The interrelationship between the spleen colony‐forming cells, the macrophage‐layer colony‐forming cells, and in vitro colony‐forming cells was discussed.

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Effect of Age of Recipient Mice on Growth and Differentiation of Transplanted Bone Marrow Cells

Cited by 16 publications

References 6 publications

Thrombocytopenic c-mpl−/− mice can produce a normal level of platelets after administration of 5-fluorouracil: the effect of age on the response

Thrombocytopenic c-mpl−/− mice can produce a normal level of platelets after administration of 5-fluorouracil: the effect of age on the response

Proliferation Activity and Number of Stromal (CFU-f) and Haemopoietic (CFUs) Stem Cells in Bone Marrow and Spleen of Rats of Different Ages

Colony‐forming Ability of Bone Marrow Cells of W Anaemic Mice on Macrophage Layer Formed in Peritoneal Cavity of Mice

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