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  • Review Article
  • Published:

Navigating the bone marrow niche: translational insights and cancer-driven dysfunction

Key Points

  • The bone marrow niche supports the integration of two major organ systems — the skeleton and the marrow

  • The niche is a unique microenvironment that is crucial for haematopoietic stem cell quiescence

  • Important features of the niche include its cellular components, hypoxia, extracellular matrices, cytokines and growth factors, and vascularization

  • Multiple myeloma and other cancer cells hijack and alter the bone marrow niche, and are altered by the niche in turn; thus, targeting niche–cancer interactions is a promising therapeutic avenue

  • Novel in vitro and in vivo models of the bone marrow niche and cancer cells enable us to better understand interactions between cancer and bone marrow niche cells

  • A more complete understanding of the biology of the unique bone marrow microenvironment must remain a major research priority

Abstract

The bone marrow niche consists of stem and progenitor cells destined to become mature cells such as haematopoietic elements, osteoblasts or adipocytes. Marrow cells, influenced by endocrine, paracrine and autocrine factors, ultimately function as a unit to regulate bone remodelling and haematopoiesis. Current evidence highlights that the bone marrow niche is not merely an anatomic compartment; rather, it integrates the physiology of two distinct organ systems, the skeleton and the marrow. The niche has a hypoxic microenvironment that maintains quiescent haematopoietic stem cells (HSCs) and supports glycolytic metabolism. In response to biochemical cues and under the influence of neural, hormonal, and biochemical factors, marrow stromal elements, such as mesenchymal stromal cells (MSCs), differentiate into mature, functioning cells. However, disruption of the niche can affect cellular differentiation, resulting in disorders ranging from osteoporosis to malignancy. In this Review, we propose that the niche reflects the vitality of two tissues — bone and blood — by providing a unique environment for stem and stromal cells to flourish while simultaneously preventing disproportionate proliferation, malignant transformation or loss of the multipotent progenitors required for healing, functional immunity and growth throughout an organism's lifetime. Through a fuller understanding of the complexity of the niche in physiologic and pathologic states, the successful development of more-effective therapeutic approaches to target the niche and its cellular components for the treatment of rheumatic, endocrine, neoplastic and metabolic diseases becomes achievable.

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Figure 1: The regenerative cells of the bone marrow niche.
Figure 2: The two mini-organs of the bone marrow niche.
Figure 3: Biochemistry of the bone marrow niche.
Figure 4: Cancer-related disruption of the bone marrow niche.
Figure 5: HSCs and tumour cells compete for the bone marrow niche.
Figure 6: The pre-metastatic niche.
Figure 7: Niche-directed carcinogenesis.

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Acknowledgements

The authors' work is supported by the NIH/NIAMS (AR066120), NIH/NIDDK (R24 DK092759-01), and by a Pilot Project Grant from NIH/NIGMS (P30GM106391) at the Maine Medical Centre Research Institute. The authors' work is also supported in part by the Department of Defence (DoD) Visionary Postdoctoral Fellowship Award, through the Peer Reviewed Cancer Research Program, under Award FY14 DoD Congressionally Directed Medical Research Programs 30 No. (W81XWH-13-1-0390); opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the DoD.

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Correspondence to Michaela R. Reagan.

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Reagan, M., Rosen, C. Navigating the bone marrow niche: translational insights and cancer-driven dysfunction. Nat Rev Rheumatol 12, 154–168 (2016). https://doi.org/10.1038/nrrheum.2015.160

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