Assay and Site of Production of Thrombopoietin

McDonald, T. P.

doi:10.1111/j.1365-2141.1981.tb07257.x

Cited by 15 publications

(5 citation statements)

References 35 publications

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“…With the concept of TPO clearly embedded in the academic conscience, laboratories run by Kelemen, Odell, McDonald, Murphy and a number of others sought to purify this illusive haematopoietic growth factor (Kelemen et al , , , ; McDonald, ,b, , , ; McDonald et al , , , ; McDonald & Nolan, ). Using urine or plasma from thrombocytopenic animals or conditioned medium from human embryonic kidney (HEK) cells, efforts were made to purify TPO using a wide variety of bioassays that had not been validated.…”

Section: Early Efforts To Purify Thrombopoietin Failedmentioning

confidence: 99%

Milestones in understanding platelet production: a historical overview

Kuter

2014

Br J Haematol

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SummaryThe discovery of thrombopoietin (TPO, also termed THPO) in 1994 was a major achievement in understanding the regulation of platelet production. In prior decades, physiological studies had demonstrated that platelets were produced from bone marrow megakaryocytes and that the megakaryocytes responded to thrombocytopenia by increasing their number, size and DNA ploidy. In 1958, it was proposed that a 'thrombopoietin' must exist that regulated this interaction between the circulating platelet mass and the bone marrow megakaryocytes. After over three decades of effort, TPO was finally purified by five independent laboratories. TPO stimulated megakaryocyte colony-forming cell growth and increased the number, size and ploidy of megakaryocytes. When the genes for TPO or TPO receptor were eliminated in mice, megakaryocytes grew and platelets were made, but at 15% of their normal number. A first generation of recombinant human (rh) TPO molecules [rhTPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rhMGDF)] rapidly entered clinical trials in 1995 and increased platelet counts in humans undergoing nonmyeloablative chemotherapy but not in those undergoing stem cell transplantation. Antibodies developed against PEGrhMGDF and development of these recombinant thrombopoietins ended. A second generation of TPO receptor agonists (romiplostim and eltrombopag) was then developed. Neither of these TPO receptor agonists demonstrated any significant untoward effects and both are now licensed in many countries for the treatment of immune thrombocytopenia. This review describes the significant experiments that have surrounded the discovery of TPO and its clinical development.

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Section: Early Efforts To Purify Thrombopoietin Failedmentioning

confidence: 99%

Milestones in understanding platelet production: a historical overview

Kuter

2014

Br J Haematol

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“…Several previous studies have shown that thrombopoietin increases both 3SS-sodium sulfate and 7Be-selenomethionine incorporation into platelets of mice [54,64,107,UO]. In these studies different thrombopoietin preparations increased 35S incorporation into platelets of mice in rebound thrombocytosis.…”

Section: Isotopic Incorpomtionmentioning

confidence: 76%

The regulation of megakaryocyte and platelet production

McDonald

1989

The International Journal of Cell Cloning

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Thrombopoietin, a hormone that regulates blood platelet production, is now recognized to be an important in vivo hematopoietic stimulator. In this concise review, the background on thrombopoietin, development of assays, and identification of sources of the hormone are summarized, along with brief descriptions of other controlling factors, sites of thrombopoietin production, results of producing antibodies against the factor, sites of action of thrombopoietin both in vitro and in vivo, and its effect on blood platelet production. Suitable assays and stable sources of thrombopoietin have now been identified and their development will permit production of recombinant material. Once the gene is cloned, it is expected that recombinant thrombopoietin will be invaluable for treating patients with several platelet production problems.

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“…Complete purification of these thrombopoietins (TPO) has yet to be accomplished, and the site and regulation of their production have not been definitely elucidated. The biological activity is defined based on in vivo effects (increased radioisotope incorporation into platelets of animals [73]). …”

Section: Humoral and Cellular Control Of Cfu-mmentioning

confidence: 99%

Human megakaryocytic progenitor cells

1987

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Megakaryocytopoiesis represents one of several differentiation pathways that hematopoietic stem cells may enter. Cells representing intermediate stages of differentiation between pluripotent stem cells and maturing megakaryocytes are called megakaryocytic progenitor cells. They are identified in human bone marrow and peripheral blood by their ability to proliferate in culture (colony forming unit-megakaryocyte, CFU-M); at some point they lose the capacity for cell division and acquire the ability for endoreduplication of DNA, a phenomenon that is unique to the megakaryocyte lineage. This review summarizes current understanding of the biology of human megakaryocytic progenitor cells, including characterization of their proliferation potentials, their antigenic determinants, and the mechanisms that govern their proliferation and maturation. Finally the involvement of CFU-M in various disorders of thrombopoiesis is discussed.

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Assay and Site of Production of Thrombopoietin

Cited by 15 publications

References 35 publications

Milestones in understanding platelet production: a historical overview

Milestones in understanding platelet production: a historical overview

The regulation of megakaryocyte and platelet production

Human megakaryocytic progenitor cells

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