HEMATOPOIETIC STEM-CELLS - EFFECT OF PRE-IRRADIATION, BLEEDING, AND ERYTHROPOIETIN ON THROMBOPOIETIC DIFFERENTIATION

Abstract

A method of measuring differentiation of stem cells towards platelets is described using syngeneic bone marrow injected into lethally irradiated mice. Fourteen days after such injection, the platelet counts are proportional to the number of bone marrow cells injected and can be used as a measure of platelet progenitors. Perturbation of the milieu in which the transplanted marrow is placed by host preirradiation, bleeding or erythropoietin administration leads to enhanced thrombopoiesis. Similar perturbation apparently favors erythropoiesis at the expense of granulopoiesis. The data from these and other experiments appear to be consistent, with a model of the stem cell compartment as a continuum with proliferative activity increasing as commitment is restricted. These functions vary inversely with the capacity for self-renewal. The various stem cell assays measure different ranges of stem cells but overlap within this continuum.