Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix

Bhushan P. Mahadik, Narayanan A.K. Bharadwaj, Randy H Ewoldt, Brendan A Harley

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)54-64
Number of pages11
JournalBiomaterials
Volume125
DOIs
StatePublished - May 1 2017

Fingerprint

Stem Cell Niche
Hydrogel
Hematopoietic Stem Cells
Stem cells
Hydrogels
Extracellular Matrix
Artificial Cells
Biocompatible Materials
Myeloid Cells
Feedback
Coculture Techniques
Cues
Cell proliferation
Biomolecules
Biomaterials
Cell Culture Techniques
Bone Marrow
Cell Proliferation
Bone
Specifications

Keywords

  • Autocrine
  • Hematopoietic
  • Hydrogel diffusivity
  • Paracrine
  • Signaling

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix. / Mahadik, Bhushan P.; Bharadwaj, Narayanan A.K.; Ewoldt, Randy H; Harley, Brendan A.

In: Biomaterials, Vol. 125, 01.05.2017, p. 54-64.

Research output: Contribution to journalArticle

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