Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities

Nat Commun. 2020 Jun 15;11(1):3025. doi: 10.1038/s41467-020-16646-2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Collagen Type VI / genetics
  • Collagen Type VI / metabolism
  • Collagen Type XII / genetics
  • Collagen Type XII / metabolism
  • Craniofacial Abnormalities / physiopathology
  • Craniofacial Abnormalities / therapy
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Osteogenesis*
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / transplantation
  • Tissue Engineering

Substances

  • Bone Morphogenetic Protein 2
  • Collagen Type VI
  • Collagen Type XII