title: Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix.
abstract: Hematopoietic stem cells (HSC) reside in unique bone marrow niches and are influenced by signals from surrounding cells, the extracellular matrix (ECM), ECM-bound or diffusible biomolecules. Here we describe the use of a three-dimensional hydrogel to alter the balance of HSC-generated autocrine feedback and paracrine signals generated by co-cultured niche-associated cells. We report shifts in HSC proliferation rate and fate specification in the presence of lineage positive (Lin+) niche cells. Hydrogels promoting autocrine feedback enhanced expansion of early hematopoietic progenitors while paracrine signals from Lin+cells increased myeloid differentiation. We report thresholds where autocrine vs. paracrine cues alter HSC fate transitions, and were able to selectively abrogate the effects of matrix diffusivity and niche cell co-culture via the use of inhibitory cocktails of autocrine or paracrine signals. Together, these results suggest diffusive biotransport in three-dimensional biomaterials are a critical design element for the development of a synthetic stem cell niche.
authors.affiliation: Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Bhushan P
authors.initials: BP
authors.lastname: Mahadik
authors.affiliation: Dept. of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Narayanan A K
authors.initials: NA
authors.lastname: Bharadwaj
authors.affiliation: Dept. of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Randy H
authors.initials: RH
authors.lastname: Ewoldt
authors.affiliation: Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Dept. of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: bharley@illinois.edu.
authors.forename: Brendan A C
authors.initials: BA
authors.lastname: Harley
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D040761:Biomimetic Materials / Q000737:chemistry; D019070:Cell Lineage / Q000502:physiology; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D019899:Paracrine Communication / Q000502:physiology*; D055153:Stem Cell Niche / Q000502:physiology*
chemical_list: D020100:Hydrogels
keywords: Autocrine; Hematopoietic; Hydrogel diffusivity; Paracrine; Signaling