Biology and clinical applications of long-term bone marrow cultures

A number of clonogenic assays for short-term bone marrow culture is now available for the quantitative analysis of the various hematopoietic progenitor cell classes. The short-term assays are not suitable to analyse either stem cell self-renewal or interactions of hematopoietic progenitors with stromal cells, especially those requiring direct cell-to-cell or cell-to-matrix contact. The technique of long-term bone marrow culture (LTBMC) allows a sustained production of myeloid cells when marrow is placed in liquid culture at relatively high cell concentration, with appropriate supplements, temperature and feeding conditions. A peculiar feature of LTBMC is that the stromal cells promote self-renewal as well as differentiation of the stem cells, without the need to add exogenous growth factors. The LTBMC system offers an approach able to investigate not only the proliferative and differentiative events but also sustained cell production and self-renewal of any clonogenic cell types. In the last years, the technique of LTBMC has been increasingly used by several groups to investigate hematopoietic regulation, stromal cell function and the interactions among stromal and hematopoietic cells. In the present report, the biology of LTBMC and their possible clinical applications will be reviewed.