Engineered vascularized bone grafts
- 2 February 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (8), 3311-3316
- https://doi.org/10.1073/pnas.0905445107
Abstract
Clinical protocols utilize bone marrow to seed synthetic and decellularized allogeneic bone grafts for enhancement of scaffold remodeling and fusion. Marrow-derived cytokines induce host neovascularization at the graft surface, but hypoxic conditions cause cell death at the core. Addition of cellular components that generate an extensive primitive plexus-like vascular network that would perfuse the entire scaffold upon anastomosis could potentially yield significantly higher-quality grafts. We used a mouse model to develop a two-stage protocol for generating vascularized bone grafts using mesenchymal stem cells (hMSCs) from human bone marrow and umbilical cord-derived endothelial cells. The endothelial cells formed tube-like structures and subsequently networks throughout the bone scaffold 4-7 days after implantation. hMSCs were essential for stable vasculature both in vitro and in vivo; however, contrary to expectations, vasculature derived from hMSCs briefly cultured in medium designed to maintain a proliferative, nondifferentiated state was more extensive and stable than that with hMSCs with a TGF-beta-induced smooth muscle cell phenotype. Anastomosis occurred by day 11, with most hMSCs associating closely with the network. Although initially immature and highly permeable, at 4 weeks the network was mature. Initiation of scaffold mineralization had also occurred by this period. Some human-derived vessels were still present at 5 months, but the majority of the graft vasculature had been functionally remodeled with host cells. In conclusion, clinically relevant progenitor sources for pericytes and endothelial cells can serve to generate highly functional microvascular networks for tissue engineered bone grafts.This publication has 41 references indexed in Scilit:
- Dose Effect of Dual Delivery of Vascular Endothelial Growth Factor and Bone Morphogenetic Protein-2 on Bone Regeneration in a Rat Critical-Size Defect ModelTissue Engineering, Part A, 2009
- Influence of Culture Medium on Smooth Muscle Cell Differentiation from Human Bone Marrow–Derived Mesenchymal Stem CellsTissue Engineering, Part A, 2009
- A Perivascular Origin for Mesenchymal Stem Cells in Multiple Human OrgansCell Stem Cell, 2008
- Engineering Robust and Functional Vascular Networks In Vivo With Human Adult and Cord Blood–Derived Progenitor CellsCirculation Research, 2008
- Bone marrow–derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculatureBlood, 2008
- Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vesselsBlood, 2008
- Extracellular matrix deposition by fibroblasts is necessary to promote capillary‐like tube formation in vitroJournal of Cellular Physiology, 2006
- Molecular regulation of vessel maturationNature Medicine, 2003
- PDGF, TGF-β, and Heterotypic Cell–Cell Interactions Mediate Endothelial Cell–induced Recruitment of 10T1/2 Cells and Their Differentiation to a Smooth Muscle FateThe Journal of cell biology, 1998
- Role of laminin and basement membrane in the morphological differentiation of human endothelial cells into capillary-like structures.The Journal of cell biology, 1988