Modulation of hematopoietic progenitor cell fate in vitro by varying collagen oligomer matrix stiffness in the presence or absence of osteoblasts

Brahmananda Reddy Chitteti, Melissa Kacena, Sherry L. Voytik-Harbin, Edward Srour

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

To recreate the in vivo hematopoietic cell microenvironment or niche and to study the impact of extracellular matrix (ECM) biophysical properties on hematopoietic progenitor cell (HPC) proliferation and function, mouse bone-marrow derived HPC (Lin-Sca1+cKit+/(LSK) were cultured within three-dimensional (3D) type I collagen oligomer matrices. To generate a more physiologic milieu, 3D cultures were established in both the presence and absence of calvariae-derived osteoblasts (OB). Collagen oligomers were polymerized at varying concentration to give rise to matrices of different fibril densities and therefore matrix stiffness (shear storage modulus, 50-800. Pa). Decreased proliferation and increased clonogenicity of LSK cells was associated with increase of matrix stiffness regardless of whether OB were present or absent from the 3D culture system. Also, regardless of whether OB were or were not added to the 3D co-culture system, LSK within 800. Pa collagen oligomer matrices maintained the highest percentage of Lin-Sca1+ cells as well as higher percentage of cells in quiescent state (G0/G1) compared to 50. Pa or 200. Pa matrices. Collectively, these data illustrate that biophysical features of collagen oligomer matrices, specifically fibril density-induced modulation of matrix stiffness, provide important guidance cues in terms of LSK expansion and differentiation and therefore maintenance of progenitor cell function.

Original languageEnglish (US)
Pages (from-to)108-113
Number of pages6
JournalJournal of Immunological Methods
Volume425
DOIs
StatePublished - Oct 1 2015

Keywords

  • Biophysical properties
  • Collagen oligomers
  • Hematopoietic stem cells
  • Matrix stiffness
  • Osteoblasts
  • Three-dimensional culture

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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