The colony stimulating factors discovery, development, and clinical applications

Abstract

HE COLONY STIMULATING FACTORS (CSFs) are four T glycoprotein regulators able to control the proliferation and differentiation of granulocytes, monocyte-macrophages, and certain related hemopoietic cells. This account will describe their discovery and characterization, discuss their actions in vitro and in vivo, the role they may play in the development of myeloid leukemia, and their current use clinically to promote hemopoietic regeneration and enhance resistance to infections in patients with cancer and other diseases. Discovery and Characterization of the CSFsThe discovery of the CSFs was made possible by the development of a semisolid culture technique able to support the proliferation and maturation of colonies of murine granulocytes and/or macrophages. This technique was developed in the mid-1960s by independent work of Bradley and Metcalf' in Melbourne and Pluznik and Sachs2 in Rehovot. In Melbourne, the culture method emerged from attempts to grow murine lymphoid leukemic cells in agar cultures. The cells failed to survive or proliferate and various underlayers of cells were added to the cultures in the hope of promoting colony formation. When normal marrow cells were used as feeder layers, colonies did develop but on inspection these were found to be in the marrow underlayer, presumably as a consequence of some influence diffusing from the layer containing the leukemic cells. Analysis showed that the colonies were composed of granulocytes and/or macrophages and the phenomenon was so remarkable that attempts to culture leukemic cells were abandoned, the culture layers reversed, and leukemic cell underlayers used to stimulate the formation from marrow cells of normal colonies. ' Further studies showed that fragments of normal organs

LIM domain only 4 protein promotes granulocyte colony-stimulating factor-induced signaling in neurons

“…Almost all growth factors display endogenous neuroprotective and neurotrophic effects on mature neurons [1]. One of the few growth factors currently approved for clinical use is the granulocyte colony-stimulating factor (GCSF), routinely prescribed to treat neutropenia (low neutrophil count in the blood) [2]. In addition, GCSF can cross the blood-brain barrier, and recent experimental studies have shown that the administration of GCSF is neuroprotective both for in vitro cultured cortical neurons and in vivo focal cerebral ischemia [3][4][5][6][7].…”

Antibiotic prophylaxis with meropenem after allogeneic stem cell transplantation

“…Different strategies, such as barrier nursing, intravenous immunoglobulins, hematopoietic growth factors and antimicrobial agents, [1][2][3][4] have been proposed in order to decrease infectious episodes among patients receiving intensive chemotherapy. The use of recombinant hematopoietic growth factors has shortened the duration of granulocytopenia and lessened the risk for infection, 5 but there is conflicting evidence concerning the efficacy of these growth factors in preventing infection-related mortality in stem cell transplanted patients. [6][7][8] In the case of antimicrobial agents, selective gut decontamination has decreased both the incidence of Gram-negative bacterial infections in neutropenic patients and the risk of acute graft-versus-host disease (aGVHD) 3,4 and, in addition, several randomized controlled trials have demonstrated a reduction of infections caused by Gram-negative bacteria by using quinolone prophylaxis in neutropenic patients.…”

Intratibial injection of an anti-doxorubicin monoclonal antibody prevents drug-induced myelotoxicity in mice

“…Autografting of peripheral blood stem cells or progenitors harvested by leukapheresis before chemotherapy can speed haematopoietic recovery (Henon et al, 1992;Roberts et al, 1992;Henon, 1993). Moreover, expansion of surviving progenitor populations and, thereby, an increased output of mature cells has recently been obtained using haematopoietic growth factors, either alone or in combination with bone marrow or peripheral blood stem cell (PBSC) reinfusion (Metcalf, 1990;Lieschke et al, 1992). Most of these haematopoietic growth factors are produced in the bone by the haematopoietic microenvironment comprised of an admixture of several adherent cell types, including fibroblasts, reticular adventitial cells and macrophages (Dexter, 1989;Eaves et al, 1991).…”