Adipocytic Cells Augment the Support of Primitive Hematopoietic Cells In Vitro But Have No Effect in the Bone Marrow Niche Under Homeostatic Conditions

Abstract

Mesenchymal stem cells (MSCs), as well as osteoblastic cells derived from these MSCs, have been shown to be key components of the hematopoietic stem cell (HSC) niche. In this study, we wished to examine whether other cell types that are known to differentiate from MSCs similarly regulate the stem cell niche, namely cells of the adipocyte lineage. Recent studies have examined the role that adipocytes play in the biology of the HSCs in different bone locations and in transplantation settings; however, none have examined their role under homeostatic conditions. We compared the ability of adipocytic and nonadipocytic cell lines to support primitive hematopoietic cells in vitro. Preadipocytic cell lines demonstrated enhanced support of hematopoietic cells. Similarly, primary bone marrow (BM) cells treated with troglitazone, a drug that enhances adipogenesis, also demonstrated augmented support over control-treated stromal cells. We further examined the effects of increased adipocyte number in vivo under homeostatic conditions using troglitazone treatment and found that these alterations had no effect on HSC frequency. Taken together, we demonstrate that cells of the adipocyte lineage promote the ability of stromal cells to support primitive hematopoietic cells in vitro, yet alterations of adipocyte number and volume in vivo have no effect. These data suggest that adipocytes are not a component of the adult BM HSC niche under homeostatic conditions.

Niche heterogeneity in the bone marrow

“…134,135 However, alterations of adipocyte number and volume in vivo have been reported to have no effect on HSCs. 134,135 …”

Marrow Adipose Tissue: Trimming the Fat

“…It remains unclear whether MAT is always a negative component of the hematopoietic niche. For example, thiazolidinedione (TZD)-induced MAT expansion in mice did not alter hematopoietic progenitor frequency within the bone marrow in vivo [46]. Future work is needed to extend these studies and to determine if MAT can serve as a supportive member of the niche or an energy source for hematopoietic differentiation in some contexts (Figure 1).…”

HSC Niche Biology and HSC Expansion Ex Vivo

“…Also, nonmyelinating Nestin+ Schwann cells have been found to activate TGF-β1-mediated inhibition of HSC self-renewal in mice [16]. Finally, murine BM adipocytes can also secrete soluble factors that inhibit HSCs self-renewal [70], with recent reports suggesting that adipocytes can support murine HSCs in-vitro , while not exhibiting any effects on HSCs in vivo [71]. Taken together, data indicate that various cytokines and growth factors derived from the BM niche are able to regulate HSC self-renewal and differentiation (table 1), but further functional characterization will be required.…”