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Sci Rep. 2016 Aug 18;6:31951. doi: 10.1038/srep31951.

Distinguishing autocrine and paracrine signals in hematopoietic stem cell culture using a biofunctional microcavity platform.

Author information

1
Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Dresden, Germany.
2
University of Toronto, Toronto, Canada.
3
TU Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.
4
Institute of Biochemistry, Universität Leipzig, Leipzig, Germany.

Abstract

Homeostasis of hematopoietic stem cells (HSC) in the mammalian bone marrow stem cell niche is regulated by signals of the local microenvironment. Besides juxtacrine, endocrine and metabolic cues, paracrine and autocrine signals are involved in controlling quiescence, proliferation and differentiation of HSC with strong implications on expansion and differentiation ex vivo as well as in vivo transplantation. Towards this aim, a cell culture analysis on a polymer microcavity carrier platform was combined with a partial least square analysis of a mechanistic model of cell proliferation. We could demonstrate the discrimination of specific autocrine and paracrine signals from soluble factors as stimulating and inhibitory effectors in hematopoietic stem and progenitor cell culture. From that we hypothesize autocrine signals to be predominantly involved in maintaining the quiescent state of HSC in single-cell niches and advocate our analysis platform as an unprecedented option for untangling convoluted signaling mechanisms in complex cell systems being it of juxtacrine, paracrine or autocrine origin.

PMID:
27535453
PMCID:
PMC4989144
DOI:
10.1038/srep31951
[Indexed for MEDLINE]
Free PMC Article

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