title: Distinguishing autocrine and paracrine signals in hematopoietic stem cell culture using a biofunctional microcavity platform.
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.
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Dresden, Germany.
authors.forename: Eike
authors.initials: E
authors.lastname: Müller
authors.affiliation: University of Toronto, Toronto, Canada.
authors.forename: Weijia
authors.initials: W
authors.lastname: Wang
authors.affiliation: University of Toronto, Toronto, Canada.
authors.forename: Wenlian
authors.initials: W
authors.lastname: Qiao
authors.affiliation: TU Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: University of Toronto, Toronto, Canada.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Zandstra
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Dresden, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Dresden, Germany.|Institute of Biochemistry, Universität Leipzig, Leipzig, Germany.
authors.forename: Tilo
authors.initials: T
authors.lastname: Pompe
mesh_terms: D019898:Autocrine Communication; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D016018:Least-Squares Analysis; D019899:Paracrine Communication; D011108:Polymers; D015398:Signal Transduction; D054457:Tissue Scaffolds
chemical_list: D011108:Polymers