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Modulating the stem cell niche for tissue regeneration

Abstract

The field of regenerative medicine holds considerable promise for treating diseases that are currently intractable. Although many researchers are adopting the strategy of cell transplantation for tissue repair, an alternative approach to therapy is to manipulate the stem cell microenvironment, or niche, to facilitate repair by endogenous stem cells. The niche is highly dynamic, with multiple opportunities for intervention. These include administration of small molecules, biologics or biomaterials that target specific aspects of the niche, such as cell-cell and cell–extracellular matrix interactions, to stimulate expansion or differentiation of stem cells, or to cause reversion of differentiated cells to stem cells. Nevertheless, there are several challenges in targeting the niche therapeutically, not least that of achieving specificity of delivery and responses. We envisage that successful treatments in regenerative medicine will involve different combinations of factors to target stem cells and niche cells, applied at different times to effect recovery according to the dynamics of stem cell–niche interactions.

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Figure 1: Composition of the niche.

Kim Caesar/Nature Publishing Group

Figure 2: Representative schema illustrating stem cell niches.

Kim Caesar/Nature Publishing Group

Figure 3: Manipulation of the hematopoietic stem cell niche in vivo.

Kim Caesar/Nature Publishing Group

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Acknowledgements

We apologize for any omissions due to space constraints. S.W.L. is supported by research funding from the National Health and Medical Research Council, the Leukaemia Foundation of Australia and the Rhys Pengelly Fellowship in Leukaemia Research. D.A.W. is supported by National Institutes of Health DK062757. F.M.W. gratefully acknowledges the financial support of the Medical Research Council and the Wellcome Trust.

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Lane, S., Williams, D. & Watt, F. Modulating the stem cell niche for tissue regeneration. Nat Biotechnol 32, 795–803 (2014). https://doi.org/10.1038/nbt.2978

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