Thrombopoietin Bioassay

The production of megakaryocytes (MKs) and platelets is a finely controlled process that maintains circulating platelet numbers within a narrow range in normal individuals while providing sufficient reserve capacity for rapid production in emergencies such as bleeding. Forty years ago, it was recognized that a humoral regulator circulating in thrombocytopenic animals was able to stimulate platelet production in normal recipients (1 ). Termed thrombopoietin (TPO), the properties of this activity were defined over subsequent years but only in the early 1990s was the cDNA encoding TPO cloned (2 –5 ). The availability of recombinant TPO allowed precise analysis of the properties of this cytokine in vitro and in vivo. These analyses, coupled with studies in mice lacking the genes for TPO or its receptor, c-Mpl, conclusively demonstrated that TPO is the major physiological regulator of steady-state platelet production (6 ,7 ). It is anticipated that the potent capacity of TPO to stimulate platelet production in vivo will allow improved clinical management of thrombocytopenia (8 ). Accordingly, TPO and related c-Mpl ligands are currently being evaluated as clinical reagents for the stimulation of platelets in thrombocytopenic patients, particularly following cytotoxic cancer treatment.