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Issue 1, 2009
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Perturbation of single hematopoietic stem cell fates in artificial niches

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Abstract

Hematopoietic stem cells (HSCs) are capable of extensive self-renewal in vivo and are successfully employed clinically to treat hematopoietic malignancies, yet are in limited supply as in culture this self-renewal capacity is lost. Using an approach at the interface of stem cell biology and bioengineering, here we describe a novel platform of hydrogel microwell arrays for assessing the effects of either secreted or tethered proteins characteristic of the in vivo microenvironment, or niche, on HSC fate in vitro. Time-lapse microscopic analyses of single cells were crucial to overcoming inevitable heterogeneity of FACS-enriched HSCs. A reduction in proliferation kinetics or an increase in asynchronous division of single HSCs in microwells in response to specific proteins (Wnt3a and N-Cadherin) correlated well with subsequent serial long-term blood reconstitution in mice in vivo. Single cells that divided once in the presence of a given protein were capable of in vivo reconstitution, providing evidence of self-renewal divisions of HSCsin vitro. These results validate the hydrogel microwell platform as a broadly applicable paradigm for dissecting the regulatory role of specific signals within a complex stem cell niche.

Graphical abstract: Perturbation of single hematopoietic stem cell fates in artificial niches

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Publication details

The article was received on 09 Sep 2008, accepted on 21 Oct 2008 and first published on 21 Nov 2008


Article type: Paper
DOI: 10.1039/B815718A
Citation: Integr. Biol., 2009,1, 59-69
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    Perturbation of single hematopoietic stem cell fates in artificial niches

    M. P. Lutolf, R. Doyonnas, K. Havenstrite, K. Koleckar and H. M. Blau, Integr. Biol., 2009, 1, 59
    DOI: 10.1039/B815718A

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