The function of adipocytes in the bone marrow stroma: an update

Gimble, Jeffrey M.; Robinson, Claudius E.; Wu, Xiying; Kelly, Katherine A.

doi:10.1016/s8756-3282(96)00258-x

Cited by 442 publications

(350 citation statements)

References 86 publications

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“…The adipocyte is the most abundant stromal cell type found in the marrow (9); however, the role of this cell in hematopoiesis has not been clearly defined. Mature adipocytes are present in longterm bone marrow cultures (10) and are capable of supporting both lymphopoiesis (11) and granulopoiesis (12).…”

Section: Identification Of Adiponectin As a Novel Hemopoietic Stem Cementioning

confidence: 99%

Identification of Adiponectin as a Novel Hemopoietic Stem Cell Growth Factor

DiMascio

Voermans²,

Uqoezwa³

et al. 2007

The Journal of Immunology

171

126

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The hemopoietic microenvironment consists of a diverse repertoire of cells capable of providing signals that influence hemopoietic stem cell function. Although the role of osteoblasts and vascular endothelial cells has recently been characterized, the function of the most abundant cell type in the bone marrow, the adipocyte, is less defined. Given the emergence of a growing number of adipokines, it is possible that these factors may also play a role in regulating hematopoiesis. Here, we investigated the role of adiponectin, a secreted molecule derived from adipocytes, in hemopoietic stem cell (HSC) function. We show that adiponectin is expressed by components of the HSC niche and its’ receptors AdipoR1 and AdipoR2 are expressed by HSCs. At a functional level, adiponectin influences HSCs by increasing their proliferation, while retaining the cells in a functionally immature state as determined by in vitro and in vivo assays. We also demonstrate that adiponectin signaling is required for optimal HSC proliferation both in vitro and in long term hemopoietic reconstitution in vivo. Finally we show that adiponectin stimulation activates p38 MAPK, and that inhibition of this pathway abrogates adiponectin’s proliferative effect on HSCs. These studies collectively identify adiponectin as a novel regulator of HSC function and suggest that it acts through a p38 dependent pathway.

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Section: Identification Of Adiponectin As a Novel Hemopoietic Stem Cementioning

confidence: 99%

Identification of Adiponectin as a Novel Hemopoietic Stem Cell Growth Factor

DiMascio

Voermans²,

Uqoezwa³

et al. 2007

The Journal of Immunology

171

126

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show abstract

“…In vitro adipocytes have been shown to be able to support myelopoiesis and lymphopoiesis and suppress human HSC differentiation, thus prolonging cell survival [12][13][14]. Additionally, adipocytes have been found to secret adipokines, cytokine family growth factors that play a role in hematopoiesis.…”

Section: Introductionmentioning

confidence: 99%

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

Spindler

Tseng

Zhou

et al. 2014

Stem Cells and Development

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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.

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“…T he fraction of bone marrow that is occupied by fat is substantial and increases with age (1,2). Fat cells derive from the same mesenchymal stem cells that give rise to the hematopoiesis supporting stromal cells in that organ and have long been suspected to influence blood cell formation (1,3).…”

mentioning

confidence: 99%

“…Fat cells derive from the same mesenchymal stem cells that give rise to the hematopoiesis supporting stromal cells in that organ and have long been suspected to influence blood cell formation (1,3). Indeed, many fat cell products, including type 1 IFNs, PGs, leptin, and sex steroids are known modulators of lymphohematopoiesis (4 -9).…”

mentioning

confidence: 99%

Adiponectin, a Fat Cell Product, Influences the Earliest Lymphocyte Precursors in Bone Marrow Cultures by Activation of the Cyclooxygenase-Prostaglandin Pathway in Stromal Cells

Yokota

Meka

Kouro

et al. 2003

The Journal of Immunology

130

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Adiponectin, an adipocyte-derived hormone, is attracting considerable interest as a potential drug for diabetes and obesity. Originally cloned from human s.c. fat, the protein is also found in bone marrow fat cells and has an inhibitory effect on adipocyte differentiation. The aim of the present study is to explore possible influences on lymphohematopoiesis. Recombinant adiponectin strongly inhibited B lymphopoiesis in long-term bone marrow cultures, but only when stromal cells were present and only when cultures were initiated with the earliest category of lymphocyte precursors. Cyclooxygenase inhibitors abrogated the response of early lymphoid progenitors to adiponectin in stromal cell-containing cultures. Furthermore, PGE2, a major product of cyclooxygenase-2 activity, had a direct inhibitory influence on purified hematopoietic cells, suggesting a possible mechanism of adiponectin action in culture. In contrast to lymphopoiesis, myelopoiesis was slightly enhanced in adiponectin-treated bone marrow cultures, and even when cultures were initiated with single lymphomyeloid progenitors. Finally, human B lymphopoiesis was also sensitive to adiponectin in stromal cell cocultures. These results suggest that adiponectin can negatively and selectively influence lymphopoiesis through induction of PG synthesis. They also indicate ways that adipocytes in bone marrow can contribute to regulation of blood cell formation.

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The function of adipocytes in the bone marrow stroma: an update

Cited by 442 publications

References 86 publications

Identification of Adiponectin as a Novel Hemopoietic Stem Cell Growth Factor

Identification of Adiponectin as a Novel Hemopoietic Stem Cell Growth Factor

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

Adiponectin, a Fat Cell Product, Influences the Earliest Lymphocyte Precursors in Bone Marrow Cultures by Activation of the Cyclooxygenase-Prostaglandin Pathway in Stromal Cells

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