Adipogenesis in a myeloid supporting bone marrow stromal cell line

Abstract

The bone marrow stroma contains pre-adipocyte cells which are part of the hemopoietic microenvironment. Cloned stromal cell lines differ both in their ability to support myeloid and lymphoid development and in their ability to undergo adipocyte differentiation in vitro. These processes have been examined in the +/+2.4 murine stromal cell line and compared to other stromal and pre-adipocyte cell lines. In long-term cultures, the +/+2.4 stromal cells support myeloid cell growth, consistent with their expression of macrophage-colony stimulating factor mRNA. However, despite the presence of mRNA for the lymphoid supportive cytokines interleukins 6 and 7, +/+2.4 cells failed to support stromal cell dependent B lineage lymphoid cells in vitro, suggesting that these stromal cells exhibit only a myelopoietic support function. The +/+2.4 cells differentiate into adipocytes spontaneously when cultured in 10% fetal bovine serum. The process of adipogenesis can be accelerated by a number of agonists based on morphologic and gene marker criteria. Following induction with hydrocortisone, methylisobutylxanthine, indomethacin, and insulin in combination, a time dependent increase in the steady state mRNA and enzyme activity levels of the following adipocyte specific genes was observed: adipocyte P2, adipsin, CAAT/enhancer binding protein, and lipoprotein lipase. In contrast, adipogenesis was accompanied by a slight decrease in the signal intensity of the macrophage-colony stimulating factor mRNA level, similar to that which has been reported in other bone marrow stromal cell lines. These data demonstrate that although the lympho-hematopoietic support function of pre-adipocyte bone marrow stromal cell lines is heterogeneous, they share a common mechanism of adipogenesis.

Influence of omega-6 PUFA arachidonic acid and bone marrow adipocytes on metastatic spread from prostate cancer

“…Adipocytes in different areas may process/store fat differently according to the role that they are supporting and although few studies have been conducted in this area, it has been reported that BM-Ad's have distinct and critical differences compared with extramedullary adipocytes (Bathija et al, 1979;Tavassoli, 1984;Gimble et al, 1992). Although the exact function of BM-Ads is unclear (Nuttall et al, 1998) they are numerous in this location, where they have a key role in haematopoiesis (Gimble et al, 1992), with cobblestone areas close to adipocytes representing active haematopoiesis. Furthermore, propagation of long term BM culture fails when adipocytes are absent, following arrest of differentiation from adipocyte precursors in steroid-free culture (Brown et al, 2006).…”

“…The precise role of BM-Ad, present in abundance in BMS, is unknown. It is hypothesised that they have a role in haematopoiesis (Gimble et al, 1992) or act as energy stores supporting oxidative metabolism of resorbing osteoclasts (Dodds et al, 1994) and are fundamental to BMS formation and its long-term maintenance (Gartner and Kaplan, 1980). In long-term human BMS/CaP models malignant cells migrate towards BM-Ad and take up lipids from adipocytes or the surrounding microenvironment (Brown et al, 2006).…”

Identification of Adiponectin as a Novel Hemopoietic Stem Cell Growth Factor

“…Mature adipocytes are present in longterm bone marrow cultures (10) and are capable of supporting both lymphopoiesis (11) and granulopoiesis (12). Additionally, following irradiation injury, adipocytes first appear after 7 days, a time point corresponding to the initiation of hemopoietic proliferation (13).…”

Adipogenesis in Nonadherent and Adherent Bone Marrow Stem Cells Grown in Fibrin Gel and in the Presence of Adult Plasma

“…Other cell culture conditions such as the use of a three-dimensional (3-D) matrix (e.g., agar, methylcellulose, fibrin or plasma clots, and collagen) [Dainiak et al, 1985;Kuriya et al, 1987;Bilko et al, 2005] have been proposed to grow and mature hematopoietic stem cells, but, in those conditions, adipogenesis was not reported. However, it has been previously reported that murine bone marrow preadipocytes are part of the hematopoietic environment [Gimble et al, 1992].…”

“…In vitro, mesenchymal stem cells are capable of differentiating into different cellspecific lineages such as bone, muscle, cartilage or fat cells, depending upon influences from various bioactive factors [Pittenger et al, 1999;Gregory et al, 2005]. One interesting feature is that adipogenesis occurs in mesenchymal cells derived from murine or human bone marrows in the presence of a mixture of dexamethasone, methylisobutylxanthine (IBMX) and insulin [Lanotte et al, 1982;Gimble et al, 1992;Pittenger et al, 1999;Song et al, 2006]. Moreover, the presence of horse serum and/ or dexamethasone [Mori et al, 1987[Mori et al, , 1989Justesen et al, 2002], rabbit serum [Diascro et al, 1998], or human plasma or serum [Lin et al, 2005] in culture media can also induce adipogenesis of bone marrow-derived cells or mesenchymal stem cells.…”