Characterization of adipose-derived mesenchymal stem cell combinations for vascularized bone engineering

Tissue Eng Part A. 2013 Jun;19(11-12):1373-85. doi: 10.1089/ten.TEA.2012.0323. Epub 2013 Mar 18.

Abstract

Since bone repair and regeneration depend on vasculogenesis and osteogenesis, both of these processes are essential for successful vascularized bone engineering. Using adipose-derived stem cells (ASCs), we investigated temporal gene expression profiles, as well as bone nodule and endothelial tubule formation capacities, during osteogenic and vasculogenic ASC lineage commitment. Osteoprogenitor-enriched cell populations were found to express RUNX2, MSX2, SP7 (osterix), BGLAP (osteocalcin), SPARC (osteonectin), and SPP1 (osteopontin) in a temporally specific sequence. Irreversible commitment of ASCs to the osteogenic lineage occurred between days 6 and 9 of differentiation. Endothelioprogenitor-enriched cell populations expressed CD34, PECAM1 (CD31), ENG (CD105), FLT1 (Vascular endothelial growth factor [VEGFR1]), and KDR (VEGFR2). Capacity for microtubule formation was evident in as early as 3 days. Functional capacity was assessed in eight coculture combinations for both bone nodule and endothelial tubule formation, and the greatest expression of these end-differentiation phenotypes was observed in the combination of well-differentiated endothelial cells with less-differentiated osteoblastic cells. Taken together, our results demonstrate vascularized bone engineering utilizing ASCs is a promising enterprise, and that coculture strategies should focus on developing a more mature vascular network in combination with a less mature osteoblastic stromal cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Adolescent
  • Adult
  • Biomarkers / metabolism
  • Bone and Bones / blood supply*
  • Bone and Bones / physiology*
  • Cell Differentiation
  • Cell Lineage
  • Coculture Techniques
  • Female
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Microtubules / metabolism
  • Middle Aged
  • Neovascularization, Physiologic*
  • Osteocytes / cytology
  • Osteocytes / metabolism
  • Osteogenesis
  • Tissue Engineering / methods*
  • Young Adult

Substances

  • Biomarkers