TY - JOUR
T1 - Engineering bone tissue substitutes from human induced pluripotent stem cells
AU - De Peppo, Giuseppe Maria
AU - Marcos-Campos, Iván
AU - Kahler, David John
AU - Alsalman, Dana
AU - Shang, Linshan
AU - Vunjak-Novakovic, Gordana
AU - Marolt, Darja
PY - 2013/5/21
Y1 - 2013/5/21
N2 - 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.
AB - 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.
KW - Bone regeneration
KW - Dynamic culture
KW - Embryonic stem cells
KW - Mesodermal progenitors
KW - Microarray analysis
UR - http://www.scopus.com/inward/record.url?scp=84878146454&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878146454&partnerID=8YFLogxK
U2 - 10.1073/pnas.1301190110
DO - 10.1073/pnas.1301190110
M3 - Article
C2 - 23653480
AN - SCOPUS:84878146454
SN - 0027-8424
VL - 110
SP - 8680
EP - 8685
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
ER -