Adrenomedullin and Endothelin-1: Two New Growth Factors for In Vitro Expansion of Hematopoietic Cord Blood Cells

Abstract

Peptides derived from pro-adrenomedullin (AM) and endothelin (ET) establish two families of regulatory factors that are almost ubiquitously expressed in human tissues. Recently, some studies demonstrated that AM is expressed by all terminal cells of the lymphoid and myeloid pathways, while endothelin-1 (ET-1) is expressed and released by normal bone marrow platelet precursor cells. Hence, we investigated the inductive capacity of these two factors on clonal growth of hematopoietic cord blood stem cells (CBSCs), culturing whole cord blood, mononucleated cells and CD34+38− subset population in the presence of high concentrations of AM, ET-1 (5 × 10−8 M) and their inhibitors (and 5 × 10−7 M). Moreover, we performed CBSCs middle-term expansion in a stroma-free liquid culture medium with AM, ET-1, and three different cytokine combinations. After 2 weeks of incubation, aliquots of expanded-cell suspensions were seeded on semisolid medium and clonogenic tests were carried out by counting the number of colony-for...