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| Status |
Public on Sep 01, 2012 |
| Title |
Engineering endochondral ossification using Sonic Hedgehog for bone regeneration |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Endochondral ossification (EO) is the natural route for the regeneration of large and mechanically challenged bone defects. Regeneration occurs via a fibrocartilagenous phase which turns into bone upon vascularization and the formation of a transient collagen type X extra cellular matrix. These two critical initiator of EO are mediated by Hedgehog proteins. We investigated a tissue engineering approach using Sonic Hedgehog (Shh) as a pleiotropic factor regulating the in vitro formation of a vascularized bone tissue precursor for in vivo endochondral bone formation. The tissue engineered graft was formed using human mesenchymal stem cells and prevascularized using human umbilical vein endothelial cells. We show that Shh induced, in vitro, the maturation of the engineered vascular network along with the expression of collagen type X which resulted, in vivo, in an improved vascularization and the rapid formation of large amounts of osteoids through EO. Osteoids further matured into, currently unmatched, clinically relevant amount of lamellar bone including osteoclasts, bone lining cells and bone marrow-like cavities. This result suggests that Hh is a master regulator of EO allowing for the formation of complex tissues with considerable therapeutic potential for bone regeneration.
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| Overall design |
The effect of Cyclopamine on expression of Hedgehog, angiogenesis and axon guidance marker genes was analyzed by seeding a coculture of 92% hMSCs and 8% huvEC supplemented or not in cyclopamine, for 12 days
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| Contributor(s) |
Rivron NC, Raiss C, Rouwkema J, Liu J, Nandakumar A, Truckenmuller R, Sticht C, Gretz N, vanBlitterswijk CA |
| Citation(s) |
22388744 |
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| Submission date |
Jun 10, 2010 |
| Last update date |
Dec 03, 2012 |
| Contact name |
Carsten Sticht |
| Organization name |
University Heidelberg
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| Department |
ZMF
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| Street address |
Theodor-Kutzer-Ufer
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| City |
Mannheim |
| ZIP/Postal code |
68169 |
| Country |
Germany |
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| Platforms (1) |
| GPL10526 |
[HG-U133_Plus_2] Affymetrix GeneChip Human Genome HG-U133 Plus 2 Array [Brainarray HGU133Plus2_Hs_ENTREZG_v12] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA127409 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE22293_RAW.tar |
51.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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