Effect of cell density on mesenchymal stem cells aggregation in RGD-alginate 3D matrices under osteoinductive conditions

Macromol Biosci. 2014 Jun;14(6):759-71. doi: 10.1002/mabi.201300567. Epub 2014 Feb 28.

Abstract

Cellular activities in 3D are differentially affected by several matrix-intrinsic and extrinsic factors. This study highlights the relevance of optimizing initial cell densities when establishing 3D cultures for specific applications. Independently of the entrapping density, MSCs cultured within RGD-alginate hydrogels showed steady-state levels of metabolic activity and were in a nearly non-proliferative state, but recovered "normal" activity levels when retrieved from 3D matrices and re-cultured as monolayers. Importantly, high-densities promoted the establishment of cell-cell contacts with formation of multicellular clusters stabilized by endogenous ECM, and also stimulated MSCs osteogenic differentiation. These MSC-ECM microtissues may be used as building blocks for tissue engineering.

Keywords: alginate hydrogels; encapsulation; self-assembly; tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry*
  • Cell Differentiation
  • Cell Line
  • Extracellular Matrix / chemistry*
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Humans
  • Hydrogels / chemistry*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Oligopeptides / chemistry*
  • Osteogenesis*
  • Tissue Engineering / methods

Substances

  • Alginates
  • Hexuronic Acids
  • Hydrogels
  • Oligopeptides
  • arginyl-glycyl-aspartic acid
  • Glucuronic Acid