Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities
Eoin P. McNeill, Suzanne Zeitouni, Simin Pan, Andrew Haskell, Michael Cesarek, Daniel Tahan, Bret H. Clough, U. Krause, Lauren K. Dobson, Mayra García, Christopher Kung, Qingguo Zhao, W. Brian Saunders, Fei Liu, Roland Kaunas, Carl A. Gregory
Abstract
Approximately 10% of fractures will not heal without intervention. Current treatments can be marginally effective, costly, and some have adverse effects. A safe and manufacturable mimic of anabolic bone is the primary goal of bone engineering, but achieving this is challenging. Mesenchymal stem cells (MSCs), are excellent candidates for engineering bone, but lack reproducibility due to donor source and culture methodology. The need for a bioactive attachment substrate also hinders progress. Herein, we describe a highly osteogenic MSC line generated from induced pluripotent stem cells that generates high yields of an osteogenic cell-matrix (ihOCM) in vitro. In mice, the intrinsic osteogenic activity of ihOCM surpasses bone morphogenic protein 2 (BMP2) driving healing of calvarial defects in 4 weeks by a mechanism mediated in part by collagen VI and XII. We propose that ihOCM may represent an effective replacement for autograft and BMP products used commonly in bone tissue engineering.