Stromal Cells in Long-Term Bone Marrow Cultures

Quesenberry, Peter J.

doi:10.1007/978-1-4612-4494-3_7

Cited by 15 publications

(6 citation statements)

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“…Long-term in vitro bone marrow culture systems which support limited myelopoiesis (Dexter cultures) or lymphopoiesis (Whitlock-Witte cultures) are dependent upon the formation of stromal cell layers. These adherent stromal cells produce several hematopoietic growth factors, albeit at low or subliminal levels, that support limited hematopoiesis [8,10,[32][33][34][35][36][37][38]. What the role of osteoblasts is in these systems is not clear [7,10].…”

Section: The Ontogeny Of Osteoblasts In the Hematopoietic Microenviromentioning

confidence: 99%

The Role of Osteoblasts in the Hematopoietic Microenvironment

1998

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Hematopoietic stem cell differentiation occurs in direct proximity to osteoblasts within the bone marrow cavity. Despite this striking affiliation, surprisingly little is known about the precise cellular and molecular impact of osteoblasts on the bone marrow microenvironment. Recently, it has been proposed that human osteoblasts support the growth of primitive human hematopoietic cells in vitro and possibly in vivo.Evidence to support this hypothesis is reviewed as follows: the influence of osteoblasts on osteoclast development; the participation of osteoblasts in long-term bone marrow cultures; the production of positive hematopoietic regulatory molecules by osteoblasts; the production of cell-cycle inhibitory factors by osteoblasts, and cellcell interactions between early hematopoietic cells and osteoblasts. Stem Cells 1998;16:7-15 STEM CELLS 1998;16:7-15

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Section: The Ontogeny Of Osteoblasts In the Hematopoietic Microenviromentioning

confidence: 99%

The Role of Osteoblasts in the Hematopoietic Microenvironment

1998

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“…extensively used to define the role of stromal cell-derived factors in hematopoiesis (ie, Dexter or Whitlock-Witte cultures). [19][20][21][22] Because many primary and transformed stromal cell lines themselves were derived from LTBMC cultures that form mineralized matrices in vitro, 23,24 the inference has been that osteoblasts must participate in stem cell activities. 25,26 An interesting early investigation demonstrated that in vivo nearly 50% of stromal cell-derived clones form bone when transplanted in vivo.…”

Section: Introduction and Historical Perspectivementioning

confidence: 99%

Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche

Taichman

2005

Blood

541

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The mechanisms of bone and blood formation have traditionally been viewed as distinct, unrelated processes, but compelling evidence suggests that they are intertwined. Based on observations that hematopoietic precursors reside close to endosteal surfaces, it was hypothesized that osteoblasts play a central role in hematopoiesis, and it has been shown that osteoblasts produce many factors essential for the survival, renewal, and maturation of hematopoietic stem cells (HSCs). Preceding these observations are studies demonstrating that the disruption or perturbation of normal osteoblastic function has a profound and central role in defining the operational structure of the HSC niche. These observations provide a glimpse of the dimensions and ramifications of HSC-osteoblast interactions. Although more research is required to secure a broader grasp of the molecular mechanisms that govern blood and bone biology, the central role for osteoblasts in hematopoietic stem cell regulation is reviewed herein from the perspectives of (1) historical context; (2) the role of the osteoblast in supporting stem cell survival, proliferation, and maintenance; (3) the participation, if any, of osteoblasts in the creation of a stem cell niche; (4) the molecules that mediate HSC-osteoblast interactions; (5) the role of osteoblasts in stem cell transplantation; and (6) Introduction and historical perspectiveHematopoiesis occurs in unique microenvironments that facilitate the maintenance of hematopoietic stem cells (HSCs) as pluripotent and support the maturation of progenitors. Each of these activities may require different growth factors and microenvironments, the identities of which have yet to be determined. In vitro, bone marrow stromal cells (BMSCs) serve as a rich source of growth factors for a variety of hematopoietic processes. BMSCs are composed of several different populations, including fibroblasts, macrophages, endothelial cells, and adipocytes. Although it is difficult to discern the relative importance of each of these cells, it has been shown that direct stromal cell-blood cell contact, BMSC production of the extracellular bone marrow matrix, and cytokine synthesis are all relevant to the formation and maturation of blood cells in vitro. [1][2][3] The role of BMSCs in vivo is less clear.Osteoblasts have long been known to play a central role in skeletal development. Derived from pluripotent mesenchymal stem cells (MSCs), they mature along a specific lineage to become highly specialized synthetic cells. As such, osteoblasts respond to many mechanical, local, and systemic stimuli that facilitate mineralization while they orchestrate bone remodeling. Osteoblasts also constitute part of the stromal cell support system in marrow, but little is known about their functional relevance to HSCs. Early attempts to understand this relationship focused on the protective function that bone might serve for the hematopoietic organ. 4 Observations in birds of recurrent trabeculation of the medullary cavity during ovulation show that the h...

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“…The most common di#erentiated product varies with the species. For murine LTBMC, these are granulocytes, macrophages and megakaryocytes (Quesenberry, 1989).…”

Section: Introductionmentioning

confidence: 99%