Bioengineered cardiac cell sheet grafts have intrinsic angiogenic potential.
Previously, we have demonstrated the long-term survival of myocardial cell sheet constructs in vivo, with microvascular network formation throughout the engineered tissues. The understanding and control of these vascularization processes are a key factor for creating thicker functional tissues. Here, we show that cardiac cell sheets express angiogenesis-related genes and form endothelial cell networks in culture. After non-invasive harvest and stacking of cell sheets using temperature-responsive culture dishes, these endothelial cell networks are maintained and result in neovascularization upon in vivo transplantation. Interestingly, we also discovered that all of the graft vessels are derived from the grafts themselves and these vessels migrate to connect with the host vasculature. Finally, blood vessel formation within the grafts can be controlled by changing the ratio of endothelial cells. In conclusion, myocardial tissue grafts engineered with cell sheet technology have their own inherent potential for the in vivo neovascularization that can be regulated in vitro.
Sekiya
Sachiko
S
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Shimizu
Tatsuya
T
Yamato
Masayuki
M
Kikuchi
Akihiko
A
Okano
Teruo
T
D000818:Animals; D000831:Animals, Newborn; D001698:Biomedical Engineering / Q000379:methods*; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D042783:Endothelial Cells / Q000166:cytology; D005786:Gene Expression Regulation; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000473:pathology; D007150:Immunohistochemistry; D008833:Microcirculation; D018919:Neovascularization, Physiologic; D009924:Organ Culture Techniques / Q000379:methods; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013696:Temperature; D023822:Tissue Engineering
D019408:Platelet Endothelial Cell Adhesion Molecule-1