The hematopoietic stem cell in its place.

Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Nature Immunology (Impact Factor: 24.97). 05/2006; 7(4):333-7. DOI: 10.1038/ni1331
Source: PubMed

ABSTRACT A signature characteristic of stem cells is their ability to self-renew, affording a theoretically limitless ability to produce daughter cells and their descendents. This near-timeless dimension of stem cell function is not free of the constraints of place. The idea that highly specialized 'microenvironmental' cues participate in the regulation of stem cells has evidence in classic embryology and more recently in adult stem cells through the use of model organisms. There is now ample evidence that an anatomically defined, specifically constituted place represents the niche for hematopoietic and other tissue-specific stem cells. This review provides a conceptual framework and detailed account of the hematopoietic stem cell niche as defined at present. The components are assembling into a more complex view of the niche and may now be amenable to examination as a system and possibly to alteration to affect outcomes in immune regeneration.

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    ABSTRACT: Since we still know very little about stem cells in their natural environment, it is useful to explore their dynamics through modelling and simulation, as well as experimentally. Most models of stem cell systems are based on deterministic differential equations that ignore the natural heterogeneity of stem cell populations. This is not appropriate at the level of individual cells and niches, when randomness is more likely to affect dynamics. In this paper, we introduce a fast stochastic method for simulating a metapopulation of stem cell niche lineages, that is, many sub-populations that together form a heterogeneous metapopulation, over time. By selecting the common limiting timestep, our method ensures that the entire metapopulation is simulated synchronously. This is important, as it allows us to introduce interactions between separate niche lineages, which would otherwise be impossible. We expand our method to enable the coupling of many lineages into niche groups, where differentiated cells are pooled within each niche group. Using this method, we explore the dynamics of the haematopoietic system from a demand control system perspective. We find that coupling together niche lineages allows the organism to regulate blood cell numbers as closely as possible to the homeostatic optimum. Furthermore, coupled lineages respond better than uncoupled ones to random perturbations, here the loss of some myeloid cells. This could imply that it is advantageous for an organism to connect together its niche lineages into groups. Our results suggest that a potential fruitful empirical direction will be to understand how stem cell descendants communicate with the niche and how cancer may arise as a result of a failure of such communication.
    PLoS Computational Biology 09/2014; 10(9):e1003794. · 4.83 Impact Factor
  • Frontiers in Bioscience 01/2010; 15(1):854. · 4.25 Impact Factor
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    ABSTRACT: Mesenchymal stromal cells (MSCs) represent a small and heterogeneous subpopulation of mesenchymal stem cells that possesses multilineage differentiation potential. These cells are mainly present in bone marrow, but also in other tissues, and represent a valuable resource for their ability to differentiate into different cell lines and for many therapeutic approaches. MSCs are able to differentiate into cells of mesodermal origin such as adipocytes, chondrocytes, osteoblasts or fibroblasts and in vitro also into cells of non-mesodermal lineages. In bone marrow, they establish the microenvironment for the growth and differentiation of the hematopoietic stem cells (HSCs) resulting crucial for HSC maintenance and haematopoiesis. Nevertheless, the proliferation and/or the survival rate of MSCs may contribute to the onset of different types of bone sarcomas, such as Osteosarcoma, Chondrosarcoma and Giant Cell Tumor of Bone that represent the result of neoplastic degeneration of their corresponding committed mesenchymal precursors, probably as a consequence of the alteration of different or common biochemical pathways.


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