Engineering bone tissue substitutes from human induced pluripotent stem cells

Giuseppe Maria De Peppo, Iván Marcos-Campos, David John Kahler, Dana Alsalman, Linshan Shang, Gordana Vunjak-Novakovic, Darja Marolt

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

Abstract

Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of our study was to evaluate the utility of human-induced pluripotent stem cells (hiPSCs) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into themesenchymal lineages and used a combination of differentiation assays, surface antigen profiling, and global gene expression analysis to identify the lines exhibiting strong osteogenic differentiation potential. We then engineered functional bone substitutes by culturing hiPSCderived mesenchymal progenitors on osteoconductive scaffolds in perfusion bioreactors and confirmed their phenotype stability in a subcutaneous implantation model for 12 wk. Molecular analysis confirmed that the maturation of bone substitutes in perfusion bioreactors results in global repression of cell proliferation and an increased expression of lineage-specific genes. These results pave the way for growing patient-specific bone substitutes for reconstructive treatments of the skeletal system and for constructing qualified experimental models of development and disease.

Original languageEnglish (US)
Pages (from-to)8680-8685
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number21
DOIs
StatePublished - May 21 2013
Externally publishedYes

Keywords

  • Bone regeneration
  • Dynamic culture
  • Embryonic stem cells
  • Mesodermal progenitors
  • Microarray analysis

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