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

Authors:
Valenzuela CD, Allori AC, Reformat DD, Sailon AM, Allen RJ Jr, Davidson EH, Alikhani M, Bromage TG, Ricci JL, Warren SM
In:
Source: Tissue Eng
Publication Date: (2013)
Issue: 19(11-12): 1373-85
Research Area:
Basic Research
Cells used in publication:
Endothelial, umbilical vein, human (HUVEC)
Species: human
Tissue Origin: vein
Osteoblast, (NHOst) human
Species: human
Tissue Origin: bone
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.