Changes of chondrocyte expression profiles in human MSC aggregates in the presence of PEG microspheres and TGF-β3

Soumya Ravindran, Jacob L. Roam, Peter K. Nguyen, Thomas M. Hering, Donald L. Elbert, Audrey McAlinden

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Biomaterial microparticles are commonly utilized as growth factor delivery vehicles to induce chondrogenic differentiation of mesenchymal stem/stromal cells (MSCs). To address whether the presence of microparticles could themselves affect differentiation of MSCs, a 3D co-aggregate system was developed containing an equal volume of human primary bone marrow-derived MSCs and non-degradable RGD-conjugated poly(ethylene glycol) microspheres (PEG-μs). Following TGF-β3 induction, differences in cell phenotype, gene expression and protein localization patterns were found when compared to MSC aggregate cultures devoid of PEG-μs. An outer fibrous layer always found in differentiated MSC aggregate cultures was not formed in the presence of PEG-μs. Type II collagen protein was synthesized by cells in both culture systems, although increased levels of the long (embryonic) procollagen isoforms were found in MSC/PEG-μs aggregates. Ubiquitous deposition of type I and type X collagen proteins was found in MSC/PEG-μs cultures while the expression patterns of these collagens was restricted to specific areas in MSC aggregates. These findings show that MSCs respond differently to TGF-β3 when in a PEG-μs environment due to effects of cell dilution, altered growth factor diffusion and/or cellular interactions with the microspheres. Although not all of the expression patterns pointed toward improved chondrogenic differentiation in the MSC/PEG-μs cultures, the surprisingly large impact of the microparticles themselves should be considered when designing drug delivery/scaffold strategies.

Original languageEnglish (US)
Pages (from-to)8436-8445
Number of pages10
JournalBiomaterials
Volume32
Issue number33
DOIs
StatePublished - Nov 1 2011

All Science Journal Classification (ASJC) codes

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

Keywords

  • Cartilage tissue engineering
  • Chondrocyte
  • Mesenchymal stem cell
  • Microsphere
  • Polyethylene
  • TGF-β

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    Ravindran, S., Roam, J. L., Nguyen, P. K., Hering, T. M., Elbert, D. L., & McAlinden, A. (2011). Changes of chondrocyte expression profiles in human MSC aggregates in the presence of PEG microspheres and TGF-β3. Biomaterials, 32(33), 8436-8445. https://doi.org/10.1016/j.biomaterials.2011.07.056