Thrombopoietin: a preclinical evaluation

Abstract

Peripheral blood cells are in majority short lived and exert a whole spectnull of actions, ranging from the transport of oxygen and carbon dioxide to the production of highly specific immunoglobulins targeted at antigens. The system is velY adaptive and substantially increased numbers of cells can be produced after, for example, major losses of blood, or in response to infections. Peripheral blood cells originate from a small population of bone marrow progenitor cells, together approximately 1.5 % of all bone marrow cells, which are morphologically nearly identical and share the expression of the CD34 antigen. (I) These cells all derive from an even smaller population of hemopoielic stem cells, which have the potential to self renew and are muliipotent. (2) Most of the slem cells in Ihe bone matTow do not actively participate in blood cell formation but remain in a quiescent state. The process from the hemopoielic stem cell to mature peripheral blood cells and several specific tissue cells, termed hematopoiesis, takes approximately 20 to 30 cell divisions, through which cells become increasingly 1110re specialized. TIlis whole process is tightly controlled by hormone like proteins, the hemopoietic growth factors or cytokines, in combination with envirOllllental influences conducted by stromal cclls and direct cell-cell contact. (2,3) Many cytokines have become known in the last 20 years, and new cytokines and cytokine receptors are still being identified. Immature cells in the bone marrow ,u-e positive for the CD34 antigen