Sonic Hedgehog-activated engineered blood vessels enhance bone tissue formation
| Autor: | Roman Truckenmüller, Jeroen Rouwkema, Carsten Sticht, Norbert Gretz, Anandkumar Nandakumar, Clemens van Blitterswijk, Nicolas C. Rivron, Jun Liu, C.C. Raiss |
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| Přispěvatelé: | Faculty of Engineering Technology |
| Rok vydání: | 2012 |
| Předmět: |
Time Factors
Mature Bone Bone Marrow Cells METIS-286512 Biology Regenerative Medicine Bone tissue Bone and Bones Bone remodeling Mice Osteogenesis Bone cell Human Umbilical Vein Endothelial Cells medicine Animals Humans Bone organ Hedgehog Proteins Sonic hedgehog Endochondral ossification Multidisciplinary Neovascularization Pathologic Tissue Engineering Cell Differentiation Anatomy Biological Sciences Blood Vessel Prosthesis Extracellular Matrix Cell biology medicine.anatomical_structure Intramembranous ossification biology.protein IR-80568 |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, 109(12), 4413-4418. National Academy of Sciences |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Large bone defects naturally regenerate via a highly vascularized tissue which progressively remodels into cartilage and bone. Current approaches in bone tissue engineering are restricted by delayed vascularization and fail to recapitulate this stepwise differentiation toward bone tissue. Here, we use the morphogen Sonic Hedgehog (Shh) to induce the in vitro organization of an endothelial capillary network in an artificial tissue. We show that endogenous Hedgehog activity regulates angiogenic genes and the formation of vascular lumens. Exogenous Shh further induces the in vitro development of the vasculature (vascular lumen formation, size, distribution). Upon implantation, the in vitro development of the vasculature improves the in vivo perfusion of the artificial tissue and is necessary to contribute to, and enhance, the formation of de novo mature bone tissue. Similar to the regenerating callus, the artificial tissue undergoes intramembranous and endochondral ossification and forms a trabecular-like bone organ including bone-marrow-like cavities. These findings open the door for new strategies to treat large bone defects by closely mimicking natural endochondral bone repair. |
| Databáze: | OpenAIRE |
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